Adrenergic Antagonists: Drugs that bind to but do not activate ADRENERGIC RECEPTORS. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters EPINEPHRINE and NOREPINEPHRINE.Adrenergic alpha-Antagonists: Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.Prazosin: A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION.Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of ERECTILE DYSFUNCTION.Adrenergic beta-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC BETA-2 RECEPTORS.Receptors, Adrenergic, alpha: One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.Adrenergic alpha-Agonists: Drugs that selectively bind to and activate alpha adrenergic receptors.Adrenergic alpha-1 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.Clonidine: An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.Idazoxan: A benzodioxane-linked imidazole that has alpha-2 adrenoceptor antagonist activity.Propanolamines: AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives.Receptors, Adrenergic: Cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction.Adrenergic alpha-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-2 RECEPTORS.Butoxamine: A beta-2 selective adrenergic antagonist. It is used primarily in animal and tissue experiments to characterize BETA-2 ANDRENERGIC RECEPTORS.Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors.Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Adrenergic beta-1 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC BETA-1 RECEPTORS.Timolol: A beta-adrenergic antagonist similar in action to PROPRANOLOL. The levo-isomer is the more active. Timolol has been proposed as an antihypertensive, antiarrhythmic, antiangina, and antiglaucoma agent. It is also used in the treatment of MIGRAINE DISORDERS and tremor.Receptors, Adrenergic, alpha-2: A subclass of alpha-adrenergic receptors found on both presynaptic and postsynaptic membranes where they signal through Gi-Go G-PROTEINS. While postsynaptic alpha-2 receptors play a traditional role in mediating the effects of ADRENERGIC AGONISTS, the subset of alpha-2 receptors found on presynaptic membranes signal the feedback inhibition of NEUROTRANSMITTER release.Medetomidine: An agonist of RECEPTORS, ADRENERGIC ALPHA-2 that is used in veterinary medicine for its analgesic and sedative properties. It is the racemate of DEXMEDETOMIDINE.Dioxanes: 1,4-Diethylene dioxides. Industrial solvents. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), dioxane itself may "reasonably be anticipated to be a carcinogen." (Merck Index, 11th ed)Phentolamine: A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of RAYNAUD DISEASE and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease.Epinephrine: The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.Adrenergic alpha-1 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-1 RECEPTORS.Doxazosin: A prazosin-related compound that is a selective alpha-1-adrenergic blocker.Receptors, Adrenergic, alpha-1: A subclass of alpha-adrenergic receptors that mediate contraction of SMOOTH MUSCLE in a variety of tissues such as ARTERIOLES; VEINS; and the UTERUS. They are usually found on postsynaptic membranes and signal through GQ-G11 G-PROTEINS.Receptors, Adrenergic, beta: One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.Phenylephrine: An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.Adrenergic alpha-2 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Adrenergic beta-Agonists: Drugs that selectively bind to and activate beta-adrenergic receptors.Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Hormone Antagonists: Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Dopamine Antagonists: Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.Neurokinin-1 Receptor Antagonists: Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Histamine H2 Antagonists: Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood.Interleukin 1 Receptor Antagonist Protein: A ligand that binds to but fails to activate the INTERLEUKIN 1 RECEPTOR. It plays an inhibitory role in the regulation of INFLAMMATION and FEVER. Several isoforms of the protein exist due to multiple ALTERNATIVE SPLICING of its mRNA.Muscarinic Antagonists: Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system.GABA Antagonists: Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.Histamine H1 Antagonists: Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.Purinergic P1 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.Piperidines: A family of hexahydropyridines.Histamine Antagonists: Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only.Nicotinic Antagonists: Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.Adenosine A2 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.Purinergic P2 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.Serotonin 5-HT3 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT3 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT3 RECEPTOR AGONISTS.Serotonin 5-HT2 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT2 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT2 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more specific 5-HT2 receptor subtypes.Adenosine A1 Receptor Antagonists: Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.Leukotriene Antagonists: A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.Angiotensin Receptor Antagonists: Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.GABA-A Receptor Antagonists: Drugs that bind to but do not activate GABA-A RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-A RECEPTOR AGONISTS.Histamine H3 Antagonists: Drugs that selectively bind to but do not activate HISTAMINE H3 RECEPTORS. They have been used to correct SLEEP WAKE DISORDERS and MEMORY DISORDERS.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Receptors, Serotonin: Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.Receptors, Endothelin: Cell surface proteins that bind ENDOTHELINS with high affinity and trigger intracellular changes which influence the behavior of cells.Receptors, N-Methyl-D-Aspartate: A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Serotonin 5-HT1 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT1 RECEPTORS, thereby blocking the actions of SEROTONIN 5-HT1 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more of the specific 5-HT1 receptor subtypes.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Dizocilpine Maleate: A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Adenosine A3 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A3 RECEPTORS.Receptor, Endothelin A: A subtype of endothelin receptor found predominantly in the VASCULAR SMOOTH MUSCLE. It has a high affinity for ENDOTHELIN-1 and ENDOTHELIN-2.Benzazepines: Compounds with BENZENE fused to AZEPINES.Biphenyl CompoundsEstrogen Antagonists: Compounds which inhibit or antagonize the action or biosynthesis of estrogenic compounds.Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.PiperazinesSulfonamides: A group of compounds that contain the structure SO2NH2.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.Serotonin Receptor Agonists: Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.Xanthines: Purine bases found in body tissues and fluids and in some plants.Purinergic P2X Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2X RECEPTORS. Included under this heading are antagonists for specific P2X receptor subtypes.Pyrazoles: Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.Peptides, Cyclic: Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).Purinergic Antagonists: Drugs that bind to and block the activation of PURINERGIC RECEPTORS.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.Azepines: Seven membered heterocyclic rings containing a NITROGEN atom.Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Cannabinoid Receptor Antagonists: Compounds that inhibit or block the activity of CANNABINOID RECEPTORS.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.PyrrolidinesTetrazolesProstaglandin Antagonists: Compounds that inhibit the action of prostaglandins.Electric Stimulation: Use of electric potential or currents to elicit biological responses.QuinoxalinesReceptors, Neurokinin-1: A class of cell surface receptors for TACHYKININS with a preference for SUBSTANCE P. Neurokinin-1 (NK-1) receptors have been cloned and are members of the G protein coupled receptor superfamily. They are found on many cell types including central and peripheral neurons, smooth muscle cells, acinar cells, endothelial cells, fibroblasts, and immune cells.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Behavior, Animal: The observable response an animal makes to any situation.Receptors, Dopamine D2: A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES.GABA-B Receptor Antagonists: Drugs that bind to but do not activate GABA-B RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-B RECEPTOR AGONISTS.Mineralocorticoid Receptor Antagonists: Drugs that bind to and block the activation of MINERALOCORTICOID RECEPTORS by MINERALOCORTICOIDS such as ALDOSTERONE.Ketanserin: A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients.Oligopeptides: Peptides composed of between two and twelve amino acids.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Receptors, Vasopressin: Specific molecular sites or proteins on or in cells to which VASOPRESSINS bind or interact in order to modify the function of the cells. Two types of vasopressin receptor exist, the V1 receptor in the vascular smooth muscle and the V2 receptor in the kidneys. The V1 receptor can be subdivided into V1a and V1b (formerly V3) receptors.Receptors, Opioid: Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.Adenosine: A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.Receptor, Cannabinoid, CB1: A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.Sialoglycoproteins: Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities.Receptors, Cholecystokinin: Cell surface proteins that bind cholecystokinin (CCK) with high affinity and trigger intracellular changes influencing the behavior of cells. Cholecystokinin receptors are activated by GASTRIN as well as by CCK-4; CCK-8; and CCK-33. Activation of these receptors evokes secretion of AMYLASE by pancreatic acinar cells, acid and PEPSIN by stomach mucosal cells, and contraction of the PYLORUS and GALLBLADDER. The role of the widespread CCK receptors in the central nervous system is not well understood.Receptors, Opioid, mu: A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.Receptor, Endothelin B: A subtype of endothelin receptor found predominantly in the KIDNEY. It may play a role in reducing systemic ENDOTHELIN levels.BenzodiazepinonesInjections, Intraventricular: Injections into the cerebral ventricles.N-Methylaspartate: An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).2-Amino-5-phosphonovalerate: The D-enantiomer is a potent and specific antagonist of NMDA glutamate receptors (RECEPTORS, N-METHYL-D-ASPARTATE). The L form is inactive at NMDA receptors but may affect the AP4 (2-amino-4-phosphonobutyrate; APB) excitatory amino acid receptors.Capsaicin: An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.Endothelin-1: A 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. (N Eng J Med 1995;333(6):356-63)Receptors, Opioid, kappa: A class of opioid receptors recognized by its pharmacological profile. Kappa opioid receptors bind dynorphins with a higher affinity than endorphins which are themselves preferred to enkephalins.Bicuculline: An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.Losartan: An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.Receptors, Purinergic P1: A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra).Receptors, Bradykinin: Cell surface receptors that bind BRADYKININ and related KININS with high affinity and trigger intracellular changes which influence the behavior of cells. The identified receptor types (B-1 and B-2, or BK-1 and BK-2) recognize endogenous KALLIDIN; t-kinins; and certain bradykinin fragments as well as bradykinin itself.Bradykinin: A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.Receptors, Neurokinin-2: A class of cell surface receptors for tachykinins that prefers neurokinin A; (NKA, substance K, neurokinin alpha, neuromedin L), neuropeptide K; (NPK); or neuropeptide gamma over other tachykinins. Neurokinin-2 (NK-2) receptors have been cloned and are similar to other G-protein coupled receptors.Receptors, Interleukin-1: Cell surface receptors that are specific for INTERLEUKIN-1. Included under this heading are signaling receptors, non-signaling receptors and accessory proteins required for receptor signaling. Signaling from interleukin-1 receptors occurs via interaction with SIGNAL TRANSDUCING ADAPTOR PROTEINS such as MYELOID DIFFERENTIATION FACTOR 88.Cholinergic Antagonists: Drugs that bind to but do not activate CHOLINERGIC RECEPTORS, thereby blocking the actions of ACETYLCHOLINE or cholinergic agonists.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Receptors, Muscarinic: One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.Gonadotropin-Releasing Hormone: A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE. GnRH is produced by neurons in the septum PREOPTIC AREA of the HYPOTHALAMUS and released into the pituitary portal blood, leading to stimulation of GONADOTROPHS in the ANTERIOR PITUITARY GLAND.Receptors, G-Protein-Coupled: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.Benzimidazoles: Compounds with a BENZENE fused to IMIDAZOLES.Histamine: An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.Cimetidine: A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.QuinuclidinesDevazepide: A derivative of benzodiazepine that acts on the cholecystokinin A (CCKA) receptor to antagonize CCK-8's (SINCALIDE) physiological and behavioral effects, such as pancreatic stimulation and inhibition of feeding.QuinolinesMuscle, Smooth: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Serotonin 5-HT4 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT4 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN RECEPTOR AGONISTS.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Receptors, Histamine H3: A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H3 receptors were first recognized as inhibitory autoreceptors on histamine-containing nerve terminals and have since been shown to regulate the release of several neurotransmitters in the central and peripheral nervous systems. (From Biochem Soc Trans 1992 Feb;20(1):122-5)Angiotensin II: An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.Isoindoles: Benzopyrroles with the nitrogen at the number two carbon, in contrast to INDOLES which have the nitrogen adjacent to the six-membered ring.Receptors, Opioid, delta: A class of opioid receptors recognized by its pharmacological profile. Delta opioid receptors bind endorphins and enkephalins with approximately equal affinity and have less affinity for dynorphins.Pyrilamine: A histamine H1 antagonist. It has mild hypnotic properties and some local anesthetic action and is used for allergies (including skin eruptions) both parenterally and locally. It is a common ingredient of cold remedies.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.Receptors, Neurotransmitter: Cell surface receptors that bind signalling molecules released by neurons and convert these signals into intracellular changes influencing the behavior of cells. Neurotransmitter is used here in its most general sense, including not only messengers that act to regulate ion channels, but also those which act on second messenger systems and those which may act at a distance from their release sites. Included are receptors for neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not located at synapses.Receptors, Corticotropin-Releasing Hormone: Cell surface proteins that bind corticotropin-releasing hormone with high affinity and trigger intracellular changes which influence the behavior of cells. The corticotropin releasing-hormone receptors on anterior pituitary cells mediate the stimulation of corticotropin release by hypothalamic corticotropin releasing factor. The physiological consequence of activating corticotropin-releasing hormone receptors on central neurons is not well understood.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Receptors, Dopamine D1: A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D1-class receptor genes lack INTRONS, and the receptors stimulate ADENYLYL CYCLASES.Receptors, Metabotropic Glutamate: Cell surface proteins that bind glutamate and act through G-proteins to influence second messenger systems. Several types of metabotropic glutamate receptors have been cloned. They differ in pharmacology, distribution, and mechanisms of action.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Mice, Inbred C57BLReceptors, Thromboxane: Cell surface proteins that bind THROMBOXANES with high affinity and trigger intracellular changes influencing the behavior of cells. Some thromboxane receptors act via the inositol phosphate and diacylglycerol second messenger systems.Dopamine Agonists: Drugs that bind to and activate dopamine receptors.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.TriazolesReceptor, Adenosine A2A: A subclass of adenosine A2 receptors found in LEUKOCYTES, the SPLEEN, the THYMUS and a variety of other tissues. It is generally considered to be a receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.Platelet Activating Factor: A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.Dopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Atropine: An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.Naphthalenes: Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Pirenzepine: An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients.Endothelins: 21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, ENDOTHELIN-1; ENDOTHELIN-2; and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides.Histamine Agonists: Drugs that bind to and activate histamine receptors. Although they have been suggested for a variety of clinical applications histamine agonists have so far been more widely used in research than therapeutically.Acetylcholine: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Vasoconstriction: The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.Tachykinins: A family of biologically active peptides sharing a common conserved C-terminal sequence, -Phe-X-Gly-Leu-Met-NH2, where X is either an aromatic or a branched aliphatic amino acid. Members of this family have been found in mammals, amphibians, and mollusks. Tachykinins have diverse pharmacological actions in the central nervous system and the cardiovascular, genitourinary, respiratory, and gastrointestinal systems, as well as in glandular tissues. This diversity of activity is due to the existence of three or more subtypes of tachykinin receptors.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Receptor, Bradykinin B2: A constitutively expressed subtype of bradykinin receptor that may play a role in the acute phase of the inflammatory and pain response. It has high specificity for intact forms of BRADYKININ and KALLIDIN. The receptor is coupled to G-PROTEIN, GQ-G11 ALPHA FAMILY and G-PROTEIN, GI-GO ALPHA FAMILY signaling proteins.Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.Receptors, Angiotensin: Cell surface proteins that bind ANGIOTENSINS and trigger intracellular changes influencing the behavior of cells.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Ritanserin: A selective and potent serotonin-2 antagonist that is effective in the treatment of a variety of syndromes related to anxiety and depression. The drug also improves the subjective quality of sleep and decreases portal pressure.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Purinergic P1 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Kinetics: The rate dynamics in chemical or physical systems.Receptor, Serotonin, 5-HT2A: A serotonin receptor subtype found widely distributed in peripheral tissues where it mediates the contractile responses of variety of tissues that contain SMOOTH MUSCLE. Selective 5-HT2A receptor antagonists include KETANSERIN. The 5-HT2A subtype is also located in BASAL GANGLIA and CEREBRAL CORTEX of the BRAIN where it mediates the effects of HALLUCINOGENS such as LSD.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Receptors, Tachykinin: Cell surface proteins that bind TACHYKININS with high affinity and trigger intracellular changes influencing the behavior of cells. Three classes of tachykinin receptors have been characterized, the NK-1; NK-2; and NK-3; which prefer, respectively, SUBSTANCE P; NEUROKININ A; and NEUROKININ B.Parasympatholytics: Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS.Cannabinoids: Compounds having the cannabinoid structure. They were originally extracted from Cannabis sativa L. The most pharmacologically active constituents are TETRAHYDROCANNABINOL; CANNABINOL; and CANNABIDIOL.
(1/217) Neural modulation of cephalexin intestinal absorption through the di- and tripeptide brush border transporter of rat jejunum in vivo.

Intestinal absorption of beta-lactamine antibiotics (e.g., cefixime and cephalexin) has been shown to proceed through the dipeptide carrier system. In a previous study, nifedipine (NFP), an L-type calcium channel blocker, enhanced the absorption of cefixime in vivo but not in vitro, and it was suggested that neural mechanisms might be involved in the effect of NFP. The aim of the present study was to assess the involvement of the nervous system on the intestinal absorption of cephalexin (CFX). To investigate this, we used a single-pass jejunal perfusion technique in rats. NFP and diltiazem enhanced approximately 2-fold the plasma levels of CFX in treated rats versus untreated controls. NFP also increased approximately 2-fold the CFX level in portal plasma and increased urinary excretion of CFX, thus indicating that CFX did effectively increase CFX intestinal absorption. Perfusing high concentrations of dipeptides in the jejunal lumen competitively reduced CFX absorption and inhibited the enhancement of CFX absorption produced by NFP. Hexamethonium and lidocaine inhibited the effect of NFP, whereas atropine, capsaicin, clonidine, and isoproterenol enhanced CFX absorption by the same order of magnitude as NFP. Thus, complex neural networks can modulate the function of the intestinal di- and tripeptide transporter. Sympathetic noradrenergic fibers, intestinal sensory neurons, and nicotinic synapses are involved in the increase of CFX absorption produced by NFP.  (+info)

(2/217) Antiadrenergic effect of chronic amiodarone therapy in human heart failure.

OBJECTIVES: The aim of the present study was to evaluate the influence of amiodarone on neurochemical parameters of sympathetic nervous activity in patients with congestive heart failure. BACKGROUND: Unlike most antiarrhythmic agents, amiodarone has been shown to exert a beneficial effect on survival in some studies of patients with congestive heart failure. The pharmacology of this agent is complex, and as such, the mode of its action is unclear in humans. Some experimental studies suggest that amiodarone exerts a sympatholytic effect. METHODS: To evaluate the effect of amiodarone on sympathetic nervous activity, we measured the total systemic and cardiac norepinephrine (NE) spillover rate by isotope dilution in 58 patients with severe heart failure (left ventricular ejection fraction 20 +/- 1%), 22 of whom were receiving chronic amiodarone treatment. Release rates for dihydroxyphenylalanine (DOPA, a precursor of NE), and endogenous and radiolabeled dihydroxyphenylglycol (DHPG and 3H-DHPG, intraneuronal metabolites of NE and 3H-NE, respectively) were also determined to assess sympathetic neuronal integrity. RESULTS: Amiodarone-treated patients had significantly lower cardiac spillover rates for NE (42%, p = 0.001), DOPA (74%, p < 0.001), DHPG (44%, p < 0.01) and 3H-DHPG (51%, p < 0.01) than those patients not treated with amiodarone. Hemodynamic assessment of amiodarone-treated patients revealed higher cardiac output (4.4 +/- 0.2 vs. 3.7 +/- 0.2 liters/min, p < 0.01), and slightly lower pulmonary capillary wedge pressure (18 +/- 2 vs. 22 +/- 1, p = NS) than in untreated patients. After correction for the potential confounding effect of hemodynamic differences, amiodarone-treated patients continued to demonstrate significantly lower spillover rates of NE, DOPA and DHPG from the heart. CONCLUSIONS: These data indicate that amiodarone may exert beneficial effects on the failing human heart through a sympatholytic process, and this action appears to be relatively cardioselective.  (+info)

(3/217) Involvement of cGMP-dependent protein kinase in adrenergic potentiation of transmitter release from the calyx-type presynaptic terminal.

I have previously reported that norepinephrine (NE) induces a sustained potentiation of transmitter release in the chick ciliary ganglion through a mechanism pharmacologically distinct from any known adrenergic receptors. Here I report that the adrenergic potentiation of transmitter release was enhanced by a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX) and by zaprinast, an inhibitor of cGMP-selective phosphodiesterase. Exogenous application of the membrane-permeable cGMP, 8-bromo-cGMP (8Br-cGMP), potentiated the quantal transmitter release, and after potentiation, the addition of NE was no longer effective. On the other hand, 8Br-cAMP neither potentiated the transmitter release nor occluded the NE-induced potentiation. The NE-induced potentiation was blocked by neither nitric oxide (NO) synthase inhibitor nor NO scavenger. The quantal transmitter release was not potentiated by NO donors, e.g., sodium nitroprusside. The NE-induced potentiation and its enhancement by IBMX was antagonized by two inhibitors of protein kinase G (PKG), Rp isomer of 8-(4-chlorophenylthio) guanosine-3', 5'-cyclic monophosphorothioate and KT5823. As with NE-induced potentiation, the effects of 8Br-cGMP on both the resting intraterminal [Ca2+] ([Ca2+]i) and the action potential-dependent increment of [Ca2+]i (DeltaCa) in the presynaptic terminal were negligible. The reduction of the paired pulse ratio of EPSC is consistent with the notion that the NE- and cGMP-dependent potentiation of transmitter release was attributable mainly to an increase of the exocytotic fusion probability. These results indicate that NE binds to a novel adrenergic receptor that activates guanylyl cyclase and that accumulation of cGMP activates PKG, which may phosphorylate a target protein involved in the exocytosis of synaptic vesicles.  (+info)

(4/217) Venous hydrostatic indifference point as a marker of postnatal adaptation to orthostasis in swine.

The postulate that venous adaptation assists postural baroreflex regulation by shifting the hydrostatic indifference point (HIP) toward the heart was investigated in eight midazolam-sedated newborn piglets. Whole body head-up (+15, +30, and +45 degrees ) and head-down (-15 and -30 degrees ) tilt provided a physiological range of orthostatic strain. HIP for all positive tilts shifted toward the heart (P < 0.05), +45 degrees HIP shifted most [6.7 +/- 0.3, 5.9 +/- 0.5, and 3.6 +/- 0.3 (SE) cm caudal to right atrium on days 1, 3, and 6, respectively]. HIP for negative tilts (3.0 +/- 0.2 cm caudal to right atrium) did not shift with postnatal age. Euthanasia on day 6 caused 2.1 +/- 0.3-cm caudal displacement of HIP for positive and negative tilts (P < 0.05). HIP proximity to right atrium was not altered by alpha-, beta-adrenoceptor and cholinoceptor blockade on day 5. It is concluded that early HIP migration reflects enhancement of venous pressure control to head-up orthostatic strain. The effect is independent of baroreflex-mediated adrenoceptor and cholinoceptor mechanisms.  (+info)

(5/217) Stimulation by transforming growth factor-alpha of DNA synthesis and proliferation of adult rat hepatocytes in primary cultures: modulation by alpha- and beta-adrenoceptor agonists.

We investigated the effects of transforming growth factor alpha (TGF-alpha) on DNA synthesis and proliferation in primary cultures of adult rat hepatocytes and examined the influence of alpha and beta adrenoceptor agonists on the TGF-alpha-induced responses. TGF-alpha (1.0 ng/ml) produced a 4.1-fold elevation of DNA synthesis during 3 h of culture and a 1.2-fold increase in the nucleus number (proliferation) during 4 h of culture at a cell density of 3.3 x 10(4) cells/cm(2). The TGF-alpha-induced hepatocyte DNA synthesis and proliferation were dose-dependent at EC(50) values of 0.36 ng/ml and 0.45 ng/ml, respectively. Hepatocyte DNA synthesis and proliferation induced by 1.0 ng/ml TGF-alpha did not reduce even at higher initial plating densities (5.0 x 10(4) and 1.0 x 10(5) cells/cm(2)). Increasing concentrations of the beta(2) adrenoceptor agonist metaproterenol (10(-7)-10(-6) M) markedly reduced the proliferative effects of TGF-alpha, whereas those of the alpha(2) adrenoceptor agonist 5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline (UK-14304; 10(-6)-10(-5) M) and the alpha(1) adrenoceptor agonist phenylephrine (10(-7)-10(-6) M) significantly potentiated the TGF-alpha action. The proliferative effects of TGF-alpha (1.0 ng/ml) were not affected significantly by a monoclonal antiepidermal growth factor receptor antibody (1-100 ng/ml) and were almost completely blocked by specific inhibitors of signal transducers such as genistein (10(-5) M), 1-6[[17beta-3methoxyestra-1,3, 5(10)-trien-17-yl]amino]hexyl]-1H-pyrrol2,5-dione (U-73122; 0(-5) M), wortmannin (5 x 10(-7) M), sphingosine (5 x 10(-6) M), 2'-amino-3'-methoxyflavone (PD98059; 5 x 10(-5) M), and rapamycin (10 ng/ml). These results suggest that among the elements that link signals of cell surface receptor to the nucleus, the proliferative action of TGF-alpha is mediated, at least, by tyrosine kinase, phospholipase C, phosphatidylinositol 3-kinase, protein kinase C, mitogen-activated protein kinase kinase, and ribosomal protein p70 S6 kinase.  (+info)

(6/217) Mechanisms of action of OPC-28326, a selective hindlimb vasodilator.

The unique cardiovascular profile of OPC-28326 [4-(N-methyl-2-phenylethylamino)-1-(3, 5-dimethyl-4-propionylaminobenzoyl)piperidine hydrochloride monohydrate] provides insight into basic mechanisms of this new drug as determined by experiments in dogs and rats. In anesthetized open-chest dogs, an i.v. administration of a low dose (0.3 and 1.0 microg/kg) of OPC-28326 selectively increased femoral artery blood flow with only minimal action on systemic blood pressure, heart rate and coronary, carotid, vertebral, renal, and mesenteric blood flows. Biochemical study suggests that OPC-28326 had no effect on phosphodiesterase-3 and -5. OPC-28326 dose-dependently inhibited phenylephrine-induced increases in blood pressure in spinally anesthetized dogs. The potency of OPC-28326 was, however, about 180 times lower than that of prazosin. Although binding studies have revealed an affinity of OPC-28326 to serotonin 5-HT(2) receptors, the drug is without effect, except at very high concentrations, on serotonin-induced contraction in an isolated canine femoral artery preparation. The potency of OPC-28326 on the increase in femoral artery blood flow was about 14 times higher than that of prazosin but was at about the same level as that obtained with yohimbine in canine autoperfused femoral artery preparations. In perfused rat hindlimb preparations, OPC-28326 inhibited the decrease in perfusion flow induced by brimonidine, a selective alpha(2)-adrenoceptor agonist. The potency of OPC-28326 was at least 10 times less than that of yohimbine. Taken together, the results show that at low doses, OPC-28326 selectively exerts a potent vasodilating effect on the femoral arterial bed, in part due to an alpha(2)-adrenoceptor-blocking activity.  (+info)

(7/217) Adrenergic and purinergic components in bisected vas deferens from spontaneously hypertensive rats.

1. Purinergic and adrenergic components of the contractile response to electrical field stimulation (EFS) have been investigated in epididymal and prostatic portions of Wystar Kyoto (WKY) and spontaneously hypertensive rat (SHR) vas deferens. 2. In both halves of SHR and WKY vas deferens, EFS (40 V, 0.5 ms for 30 s, 0.5-32 Hz) evoked frequency-related contractions. The neurogenic responses were biphasic, consisting of a rapid non-adrenergic response, dominant in the prostatic portion, followed by a slow tonic adrenergic component, dominant in the epididymal half. 3. Phasic and tonic components of the frequency-response curves evoked by EFS were significantly higher in the epididymal but not in the prostatic portion of vas deferens from SHR compared to WKY rats. 4. The alpha1-adrenoceptor antagonist prazosin (0.1 microM) was more effective against both components of the contractile response in the epididymal end of SHR than in WKY rats. 5. Inhibition by alpha, beta-methylene adenosine 5'-triphosphate (alpha,beta-meATP 3 and 30 microM) was higher in both components of the contractile responses in WKY preparations than in SHR. 6. Combined alpha1-adrenoceptor and P2x-purinoceptor antagonism virtually abolished the EFS-evoked contractile response in both strains. The degree of inhibition by prazosin (0.1 microM) after P2x-purinoceptor blockade was higher in SHR than in WKY rats. 7. These results demonstrate a modification in the purinergic and noradrenergic contribution to neurogenic responses in SHR and WKY animals besides a co-participation of ATP and noradrenaline in both contractile components of the response to EFS.  (+info)

(8/217) S18327 (1-[2-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)piperid-1-yl]ethyl]3-phenyl imidazolin-2-one), a novel, potential antipsychotic displaying marked antagonist properties at alpha(1)- and alpha(2)-adrenergic receptors: I. Receptorial, neurochemical, and electrophysiological profile.

S18327 displayed modest affinity for human (h)D(2) and hD(3) receptors and high affinity for hD(4) receptors. At each, S18327 antagonized stimulation of [(35)S]guanosine-5'-O-(3-thio)triphosphate binding by dopamine (DA). It also blocked activation of mitogen-activated protein kinase at hD(3) receptors. The affinity of S18327 at hD(1) and hD(5) sites was modest. S18327 showed pronounced affinity for human serotonin (h5-HT)(2A) receptors and human alpha(1A)-adrenergic receptors (hARs), at which it antagonized increases in intracellular Ca(2+) concentration levels elicited by 5-HT and norepinephrine (NE), respectively. S18327 presented significant affinity for halpha(2A)-ARs and antagonized NE-induced[(35)S]guanosine-5'-O-(3-thio)triphosphate binding both at these sites and at alpha(2)-ARs in rat amygdala. Reflecting blockade of alpha(2)-autoreceptors, S18327 enhanced firing of adrenergic neurons in locus ceruleus, accelerated hippocampal synthesis of NE, and increased dialysate levels of NE in hippocampus, accumbens, and frontal cortex. S18327 abolished inhibition of ventrotegmental area-localized dopaminergic neurons by apomorphine. However, S18327 alone did not affect their activity and only modestly enhanced cerebral turnover of DA and dialysate levels of DA in striatum and accumbens. In contrast, S18327 markedly increased dialysate levels of DA in frontal cortex, an action abolished by the selective alpha(2)-AR agonist, S18616. Finally, S18327 reduced synthesis and dialysate levels of 5-HT in striatum and suppressed firing of dorsal raphe-localized serotonergic neurons, an action attenuated by the alpha(1)-AR agonist cirazoline. In conclusion, S18327 possesses marked antagonist activity at alpha(1)-ARs and D(4) and 5-HT(2A) receptors and less potent antagonist activity at alpha(2)-ARs and D(1) and D(2) receptors. Antagonism by S18327 of alpha(2)-ARs enhances adrenergic transmission and reinforces frontocortical dopaminergic transmission, whereas blockade of alpha(1)-ARs inhibits dorsal raphe-derived serotonergic pathways. As further described in the accompanying paper, this profile of activity may contribute to the potential antipsychotic properties of S18327.  (+info)

*  Norepinephrine
ISBN 1-4684-3171-4. Griffith RK (2013). "Chapter 10: Adrenergic Receptors and Drugs Affecting Adrenergic Neurotransmission". In ... In most cases when the term "alpha blocker" is used without qualification, it refers to a selective alpha-1 antagonist. ... These are sympatholytic drugs that block the effects of beta adrenergic receptors while having little or no effect on alpha ... These are sympatholytic drugs that block the effects of adrenergic alpha receptors while having little or no effect on beta ...
*  Alpha blocker
Beta blocker Adrenergic antagonists Katzung, Bertram; Masters, Susan (2013). Basic and Clinical Pharmacology. Lange. ISBN 978-0 ... Non-selective α-adrenergic receptor antagonists include: Phenoxybenzamine Phentolamine Tolazoline Trazodon Selective α1- ... are a class of pharmacological agents that act as antagonists on α-adrenergic receptors (α-adrenoceptors). Historically, alpha- ... adrenergic receptor antagonists include: Alfuzosin Doxazosin Prazosin (inverse agonist) Tamsulosin Terazosin Silodosin ...
*  Phentolamine
... (Regitine) is a reversible nonselective α-adrenergic antagonist. Its primary action is vasodilation due to α1 ... In response, the β1 adrenergic receptors on the heart increase its rate, contractility, and dromotropy, which help to offset ... as they can cause unopposed α-adrenergic mediated coronary vasoconstriction, worsening myocardial ischemia and hypertension. It ...
*  Adrenergic antagonist
The α-adrenergic antagonists have different effects from the β-adrenergic antagonists. Adrenergic ligands are endogenous ... While a only a few α-adrenergic antagonists are competitive, all β-adrenergic antagonists are competitive antagonists. ... an α1-adrenergic antagonist will result in vasodilation. Some adrenergic antagonists, mostly β antagonists, passively diffuse ... An adrenergic antagonist is a drug that inhibits the function of adrenergic receptors. There are five adrenergic receptors, ...
*  Beta-2 adrenergic antagonist
A Beta-2 adrenergic antagonist (β2-adrenoceptor antagonist) is an adrenergic antagonist which blocks the beta-2 adrenergic ... ICI-118,551 Butaxamine Propranolol Betablocker Beta-2 adrenergic receptor Beta2-adrenergic agonist Bilski, AJ; Halliday, SE; ... an antagonist for β2 and for β1 or β3 adrenoceptors) like the non-selective betablocker Propranolol. ... Fitzgerald, JD; Wale, JL (1983). "The pharmacology of a beta 2-selective adrenoceptor antagonist (ICI 118,551)". J Cardiovasc ...
*  Beta-3 adrenergic antagonist
A Beta-3 adrenergic antagonist (β3-adrenoceptor antagonist) is an adrenergic antagonist which blocks the Beta-3 adrenergic ... adrenergic receptor antagonists". The Journal of Pharmacology and Experimental Therapeutics. 290 (2): 649-55. PMID 10411574. ... SR 59230A Carvedilol Betablocker Beta-3 adrenergic receptor Candelore MR, Deng L, Tota L, Guan XM, Amend A, Liu Y, Newbold R, ... an antagonist for β3 and for β1 or β2 adrenoceptors) like the non-selective betablocker Carvedilol. ...
*  Brefonalol
... is a beta-adrenergic antagonist. Halabi, A; Endell, W; Halabi, I; Kirch, W (1990). "Hemodynamic effects of ...
*  Bucumolol
... is a beta-adrenergic antagonist. Nakayama, K; Oshima, T; Koike, H (1981). "Assessment of beta-blockade and the non- ... specific effect of bucumolol, a beta-adrenergic blocking agent, on atrioventricular conduction in anesthetized dogs". Archives ...
*  Moxisylyte
It is an α1-adrenergic antagonist. In the United Kingdom, Moxisylte is marketed as Opilon (Archimedes Pharma UK Ltd) and is ...
*  Metazosin
... is an antihypertensive alpha-adrenergic antagonist. Trcka, V; König, J; Mácová, S; Smíd, M; Helfert, I; Votavová, M; ... a novel alpha-adrenergic antagonist". Biopharmaceutics & drug disposition. 10 (6): 581-9. PMID 2575403. ...
*  Cetamolol
... is a beta adrenergic antagonist. Cardioselective b1-adrenergic blocker. Klausner, MA; Irwin, C; Mullane, JF; Shand, ...
*  Bornaprolol
... is a beta-adrenergic antagonist. Cheymol, G; Jaillon, P; Lecoq, B; Lecoq, V; Cheymol, A; Krumenacker, M (1987). " ... "Cardiovascular beta-adrenergic blocking effects of bornaprolol in humans: Relation to dose and plasma concentration". Journal ...
*  Bunitrolol
... is a beta-adrenergic antagonist. Haddad, S; Poulin, P; Funk, C (2010). "Extrapolating in vitro metabolic ...
*  Levomoprolol
... is a beta adrenergic antagonist. It is the (S)-enantiomer of moprolol. Gianesello, V; Brenn, E; Figini, G; ...
*  Dorzolamide/timolol
Timolol is a non-selective beta-adrenergic antagonist. Common adverse effects include temporarily blurred vision, cloudy vision ...
*  Diprafenone
... is an antiarrhythmic beta adrenergic antagonist. Koytchev, R; Alken, RG; Mayer, O; Smith, I; Greenwood, M (1996). " ...
*  Piribedil
Dopamine receptor antagonist, selective for subtypes D4. Adrenergic receptor antagonist, subtypes α2A and α2C: could be the ... It also has α2-adrenergic antagonist properties. Treatment of Parkinson's disease (PD), either as monotherapy (without levodopa ... Dopamine antagonists reduce the effect of piribedil. At very high doses, piribedil has an emetic action on the chemoreceptor ... Agonist and Antagonist Properties at Subtypes of Dopamine D2-Like Receptor and α1/α2-Adrenoceptor" (PDF). J. Pharmacol. Exp. ...
*  Synephrine
... β2 antagonist): 3.58 μM; SR-5923A (β3 antagonist): 17 μM. The binding of racemic synephrine to cloned human adrenergic ... An adrenergic antagonist selective for α1 receptors. Reversal of reserpine-induced hypothermia by a drug is a classical test ... Referred to here as "oxedrine". A drug often used as a selective 5-HT2A antagonist. Used as a non-selective β-antagonist ... a standard α1 antagonist) and ketanserin, with prazosin being the more potent antagonist (pA2 = 9.38, vs pA2 = 8.23 for ...
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... is an alpha-1 adrenergic antagonist. Terazosin Chiang, J; Hermodsson, G; Oie, S (1991). "The effect of alpha 1-acid ... glycoprotein on the pharmacological activity of alpha 1-adrenergic antagonists in rabbit aortic strips". The Journal of ...
*  Allium neapolitanum
... seems to have beta-adrenergic antagonist properties. The Plant List "BSBI List 2007". Botanical Society of ...
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Adverse experience with cimetidine and safety of beta-adrenergic antagonists". Arch Intern Med. 145 (12): 2197-200. doi:10.1001 ...
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... is an adrenergic antagonist with antiarrhythmic and antihypertensive properties. C.R. Ganellin, David J. Triggle ( ...
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... is a beta-adrenergic antagonist, or beta blocker. Typically moprolol is prescribed to treat hypertension, high blood ...
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Medications, including aspirin, β-adrenergic antagonists (beta blockers), ibuprofen, and penicillin. Food allergies such as ... Szentivanyi's Beta Adrenergic Theory is a citation classic using the Science Citation Index and has been cited more times than ... In 1968 Andor Szentivanyi first described The Beta Adrenergic Theory of Asthma; in which blockage of the Beta-2 receptors of ... Szentivanyi, Andor (1968). "The Beta Adrenergic Theory of the Atopic Abnormality in Asthma". J. Allergy. 42: 203-232. doi: ...
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... is an α1 adrenergic agonist and an α2 adrenergic antagonist". Journal of Pharmacology and Experimental Therapeutics ... a partial agonist at both the α1B and α1D adrenergic receptors, and a nonselective antagonist to the α2 adrenergic receptor. It ... Cirazoline is a full agonist at the α1A adrenergic receptor, ...
*  List of investigational anxiolytics
... α1-adrenergic, α2-adrenergic, and H1 receptor antagonist [10] Cyclobenzaprine (TNX-102) - undefined mechanism of action [11] ... and α1-adrenergic receptor antagonist [12] Midomafetamine (MDMA; "ecstasy") - serotonin-norepinephrine-dopamine releasing agent ... 5-HT2A receptor antagonist [18] Verucerfont (GSK-561679, NBI-77860) - CRF1 receptor antagonist [19] Vilazodone (EMD-68843, SB- ... Agomelatine (AGO-178; Valdoxan) - melatonin MT1 and MT2 receptor agonist, 5-HT2C receptor antagonist[1] Riluzole sublingual ( ...
*  The Moscow International Medical Cluster
"Identification of adenylate cyclase-coupled beta-adrenergic receptors with radiolabeled beta-adrenergic antagonists". ...
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A compound selected from the group consisting of those having the formula: ##STR1## and pharmaceutically acceptable acid addition salts thereof, wherein R1 and R4 are independently selected from the group consisting of H and alkyl radicals containing 1 to 4 carbon atoms, R2 and R3 are independently selected from the group consisting of H, oxo, and alkyl radicals containing 1 to 4 carbon atoms, the 2-imidazolin-2-ylamino group may be in any of the 5-, 6-, 7- or 8- positions of the quinoxaline nucleus, and R5, R6 and R7 each is located in one of the remaining 5-, 6-, 7- or 8- positions of the quinoxaline nucleus and is selected from the group consisting of Cl, Br, H and alkyl radicals containing 1 to 3 carbon atoms. Such compounds, when administered to a mammal, provide desired therapeutic effects, such as alteration in the rate of fluid transport in the gastrointestinal tract, reduction in intraocular pressure, and increase in renal fluid flow
Índice A B C D E F G H I J K L M N Ñ O P Q R S T U V W X Y Z Eugenia abbreviata Urb. Eugenia aboukirensis Eugenia acapulcensis Steud. Eugenia aceitillo Urb.. Eugenia acrantha {Urb. Eugenia acrensis McVaugh Eugenia acrisepala Govaerts Eugenia acunae Alain Eugenia acutissima Urb. & Ekman Eugenia adenantha O.Berg Eugenia adenocarpa O.Berg Eugenia aerosa McVaugh Eugenia aeruginea DC. Eugenia afzelii Engl. Eugenia agathopoda Diels Eugenia aherniana C.B.Rob. Eugenia alagoensis (O.Berg) Mattos Eugenia alainii Borhidi Eugenia alaotrensis H.Perrier Eugenia albicans (O.Berg) Urb. Eugenia albimarginata Urb. & Ekman Eugenia alnifolia McVaugh Eugenia aloysii C.J.Saldanha Eugenia alpina (Sw.) Willd. Eugenia amatenangensis Lundell Eugenia ambanizanensis N.Snow Eugenia amblyophylla Urb. Eugenia amblyosepala McVaugh Eugenia amoena Thwaites Eugenia amplifolia Urb. Eugenia amshoffiae McVaugh Eugenia anafensis Urb. Eugenia analamerensis H.Perrier Eugenia anastomosansDC. Eugenia ancorifera Amshoff Eugenia ...
The synthesis of (2R,S)-1-(6-methoxy-4-(methoxymethyl)-1H-indol-5-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol and (2R,S)-1-(4-methoxy-6-(methoxymethyl)-1H-indol-5-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol is described. The compounds were tested for electrographic, antiarrhythmic, hypotensive, and spasmolytic activity, as well as for a1-, a2- and β1-adrenoceptor binding affinity.
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Adrenergic Antagonists- Pipeline Insights, 2015, provides the in-depth analysis of the pipeline assets across the Adrenergic Antagonists. The main objective of this report to track competitor pipeline molecules, related research activities, technology, collaborations, in-licensing and out-licensing deals.
Tweet Eugenia ball is another variety of Eugenia plants that is also known as Australian brush-cherry. It is a tall and narrow plant with dark green leaves. Eugenia ball plants are usually found in a container or in a large […]
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This paper present ultraviolet-visible absorption spectra of imazamethabenz-methyl (IMBM) (mixture of the isomers methyl 6-[(RS)-4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl]-m-toluate, m-imazamethabenz, and methyl 2-[(RS)-4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl]-p-toluate, p-imazamethabenz) and the corresponding carboxylic acid, imazamethabenz-acid (IMBA). The spectral characteristics are determined as functions of the pH. The appreciable absorbance in the visible (or near-ultraviolet) region of the spectra indicates ...
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Im afraid theres no built-in Eugenia annotation that would allow you to specify this, so Id suggest posting a question to the GMF forum. If it turns out that this that can be controlled through one of the gmf* models, you could write a polishing transformation [1] to automate this ...
Hello Lili R, could you give an example of how you build the groups, I wanted to do that but I dont know how, so I just use a ECore2GMF.eol file to reorder the objects on the palette but it does not work after some modifications to my emf file. If you know how to fix that could be great. Thanks in advance ...
A sweeping debut novel, inspired by the life of the authors mother, about a young woman who dares to fight for a brighter future in occupied KoreaIn early-t...
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Im having trouble understanding the code. But I tried to follow the instruction. I cant seem to find org.eclipse.ui.dialogs.ResourceListSelectionDialog in org.eclipse.ui.dialogs.... (the jar that is used is org.eclipse.ui.workbench_3.6.1.M20100826-1330.jar ...
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هدف از این مطالعه بررسی اثر اسانس گل میخک بارگذاری شده بر نانو ذراتآهن روی شاخصهای آنزیمی و بافت شناسی ماهی قزل آلای رنگین کمان میباشد. در بررسی حاضر 64 عدد ماهی قزل آلایرنگین کمان با میانگین وزن 24±155/8 در چهار گروه دسته بندی شدند. 3 گروه از ماهیان با غلظت های 2،25 و 50 قسمت در میلیون اسانس گل میخک بارگذاری بر نانوذرات آهن بیهوش شدندو گروه چهارم به عنوان گروه شاهد در نظر گرفته شد. زمان های رسیدن به مراحلمختلف بیهوشی اندازه گیری و ثبت شد. ماهیان پس از بیهوش شدن به تانک هایجداگانه منتقل شده و در ساعات 3 و 24 پس از بیهوشی از گروه های مختلف به شیوهقطع ساقه دمی خون گیری به
Four 2-amino-3-methylimidazo[4,5-b][1,x]naphthyridines, x = 5-8 (6-9) have been obtained from aromatic aldehydes (11-14) and 2-amino-1-methyl-2-imidazolin-5-one (15) in one step. The N-1 - and N-3 -methyl isomers of 2-aminoimidazo-[4,5-b]quinoline (5 and 10) were prepared from 2-nitrobenzaldehyde via the isolated E-isomers of imidazolin-5-one (17) and imidazolin-4-one (20).. ...
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From John A. Bushnell to Eugenia Bronaugh [page 1] Calhoun MO July 8th 1864 My Dear Eugenia Yours of the [MS. illegible] was rec[.] and was a pleasant treat. I was in hopes I could come down this evening or tomorrow, but it is not prudent to do so at this time[.] I have tried to work all day but could not, for thinking of how patriotic men can be, and how strange men can act. There will be two companies of Citizen Guards at this place[.] whether this is a good plan or the best thing to do I will not discuss. As to who are conservative, who [reble?] & who something else, I will not say[.] I understand Dr. Holland & Lieut[.] Rollins are excluded ...
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As described in the accompanying paper, the novel ligand S18327 (1-{2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperid-1-yl]ethyl}3-phenyl imidazolin-2-one) displays pronounced antagonist properties at α1-adrenergic receptors (ARs), serotonin [5-hydroxytryptamine (5-HT)2A], and D4 receptors, as well as less potent antagonist actions at α2-AR and D1and D2 receptors. Interestingly, the α2-AR antagonist properties of S18327 underlie a generalized enhancement of cerebral adrenergic transmission and a preferential facilitation of the activity of frontocortical compared with subcortical dopaminergic pathways. On the other hand, the inhibitory influence of S18327 on the activity of serotonergic neurons originating in the dorsal raphe nucleus may be attributed to its antagonist actions at α1-ARs. Notably, S18327 only weakly accelerates striatal turnover of dopamine (DA). In light of these observations, in the present study we examined the activity of S18327 in paradigms predictive of the control of ...
When using this server please cite the following paper:. Zsila F, Bikadi Z, Malik D, Hari P, Pechan I, Berces A, Hazai E.. Evaluation of drug-human serum albumin binding interactions with support vector machine aided online automated docking.. Bioinformatics. 2011 May 18. ...
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The lack of authentic standards limits the quantitative analysis of herbal drugs in biological samples. This present work demonstrated a practicable assay of herbs and their metabolites independent of the availability of authentic standards. A liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method for the qualitative and quantitative determination of the metabolites after oral administration of Evodiae fructus and Zuojinwan preparation in rat urine has been developed. Urine samples extracted with a protein precipitation procedure were separated on a C18 column using a mixture of water (containing 0.1% formic acid) and acetonitrile (30:70, v/v) as mobile phase. The detection was performed by MS with electrospray ionization interface in positive selected reaction monitoring (SRM) mode. One urine sample after administration was selected as standard. The method validation was carried out according to a conventional method that was calibrated by authentic standards. The fully
Arotinolol (INN, marketed under the tradename Almarl) is a medication in the class of mixed alpha/beta blockers. It also acts as a β3 receptor agonist. A 1979 publication suggests arotinolol as having first been described in the scientific literature by Sumitomo Chemical as "β-adrenergic blocking, antiarrhythmic compound S-596". It is used in the treatment of high blood pressure and essential tremor. Recommended dosage is 10-30 mg per day. Zhao, Jin; Golozoubova, Valeria; Cannon, Barbara; Nedergaard, Jan (July 2001). "Arotinolol is a weak partial agonist on beta 3-adrenergic receptors in brown adipocytes". Can J Physiol Pharmacol. 79 (7): 585-593. doi:10.1139/cjpp-79-7-585. PMID 11478592. Takahashi, H; Yoshida, T; Nishimura, M; Nakanishi, T; Kondo, M; Yoshimura, M (September 1992). "Beta-3 Adrenergic Agonist, BRL-26830A, and Alpha/Beta Blocker, Arotinolol, Markedly Increase Regional Blood Flow in the Brown Adipose Tissue in Anesthetized Rats". Japanese Circulation Journal. 56 (9): 936-42. ...
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Product Description Hot Sale Synephrine steroid for Losing Weight CAS 94-07-5 chemical Synephrine Details: CAS: 94-07-5 MF: C9H13NO2 MW: 167.21 EINECS: 202-300-9 Appearance: Light yellow to off-white fine powder Usage: used for rising blood pressure Product Categories: Plant Extract Synonyms: oxedrine;Synephrine;(+/-)-SYNEPHRINE;SYNEPHRINE;4-hydroxy-alpha-(methylaminomethyl)benzyl alcohol;AKOS NCG1-0008;1-[4-HYDROXYPHENYL]-2-METHYLAMINOETHANOL;AURORA KA-6561 Description: Synephrine is a kind of biological active substance, mainly extracted from the…
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If given by the intra-arterial route, the immediate effect of the hydrogenated alkaloids of ergot is unpredictable. Vasodilation is obtained in some patients only. However, it was found that in those cases who do not react, the vessels respond more easily to the release of sympathetic tone, proving that, nevertheless, the drug has had an (potential) effect, probably on the neurovascular apparatus. This effect could be demonstrated for many hours and is, therefore, of considerable therapeutic interest. Even with the higher local concentrations possible by the intra-arterial route, the hydrogenated alkaloids of ergot still did not exhibit any adrenolytic action on the peripheral blood vessels in man.. ...
Substitution reactions of (E)-11-(3-bromopropylidene)-6,11-dihydrodibenzo[b,e]thiepin (VIIIa) and its 2-chloro derivative VIIIb with 1-(2-hydroxyethyl)piperazine gave the title compounds IIIa and IIIb which afforded by treatment with acetic anhydride, decanoyl chloride and 3,4,5-trimethoxybenzoyl chloride the esters IVab-VIab. Reduction of the olefinic compounds IIIa and IIIb with hydrolytic acid resulted in the saturated amines IXa and IXb. The piperazine derivativeX was obtained by a substitution reaction of 2,11-dichloro-6,11-dihydrobenzo[b,e]thiepin with 1-(2-hydroxyethyl)piperazine. The amino alcohols IIIa and IIIb, as well as their acetates and 3,4,5-trimethoxybenzoates, are almost devoid of the CNS effects. The decanates Va and Vb have not the properties of the depot antipsychotics (neither antidepressants, nor neuroleptics). The saturated amino alcohol IXa showed some antihistamine, spasmolytic and adrenolytic effects.. ...
Atipamezole HCl is a selective ??2-adrenergic receptor antagonist (Ki values are 1.1, 1.0, 0.89, 1300 and 6500 nM for ??2A, ??2B, ??2C, ??1A and ??1B receptors respectively). Has been shown to be a brain penetrant.
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Horace Gould returns to St. Simons and wins the heart of lovely neighbor Deborah Abbott, who adores her Mr. Gould, despite the difference in their years. She is not concerned with his rumored past, but she is saddened by his lack of faith.
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Facial beauty is the combination of facial features, proportion, and harmony. When the balance is pleasing, the face is attractive. When features are out of proportion, the eye tends to consider them unattractive. Well-defined, balanced facial features and facial contours are considered a sign of beauty. Facial implants can achieve these goals.. People seek correction for facial features such as a weak chin, flat cheekbones, round face, a narrow jaw line or pointed chin. It is important to correctly analyse the magnitude of the nasal profile, the size and shape of the cheekbones, or angularity of the jaw line for the overall impact they exert on facial beauty. For example, a stronger nose will accentuate a weak chin. Small cheekbones make the nose appear larger, and a square jaw line diminishes the significance of the upper part of the face.. Facial implants are contoured to fit onto the natural bone structure. Different size implants are available and made from various materials. They may ...
There is a big difference in the effects of Synephrine vs Ephedra. Synephrine is known for its adrenergic effects, which last longer than norepinephrine. The adrenergic effects are increased cognition and power and overall body performance because of an adrenaline rush. Various scientific studies have shown that Synephrine provides cardio-vascular effects. The most prominent feature is that it increases the systolic blood pressure and pulse rate, but it does not affect the diastolic pressure at all. The effects of Synephrine are quite immediate, coming up within five minutes following the injection, and last for about an hour. Respiration is not affected by the treatment.. Synephrine is popularly used in weight-loss dietary supplements, either as a pure extract or as an additional ingredient to the main formula - it is most commonly combined with caffeine for weight loss. However, there is no real effect for weight loss that Synephrine can provide. It only slightly increases the heart rate, and ...
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Eugenia Cooney is the Greenwich, Connecticut, YouTube star who is the subject of a petition to have her removed from social media due to her perceived eating disorder.
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Eugenia Chan MD is a Pediatrician who practices in Boston, MA. Get a full report about this doctors background by clicking here.
Eugenia Piscitiello, nee Meglio, beloved wife of the late Joseph; dear sister of Mary (Adolph) Gatta, late Gena Reboletti and the late Emil (Louise) Meglio; fond godmother of many; dear aunt and
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All models were 18 years of age or older at the time of depiction. www.erotiquemonde.com has a zero-tolerance policy against illegal pornography. All content provided by Third Party Tube Sites ...
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The amniote organizer (Hensens node) can induce a complete nervous system when grafted into a peripheral region of a host embryo. Although BMP inhibition has been implicated in neural induction, non-neural cells cannot respond to BMP antagonists unless previously exposed to a node graft for at least 5 hours before BMP inhibitors. To define signals and responses during the first 5 hours of node signals, a differential screen was conducted. Here we describe three early response genes: two of them, Asterix and Obelix, encode previously undescribed proteins of unknown function but Obelix appears to be a nuclear RNA-binding protein. The third is TrkC, a neurotrophin receptor. All three genes are induced by a node graft within 4-5 hours but they differ in the extent to which they are inducible by FGF: FGF is both necessary and sufficient to induce Asterix, sufficient but not necessary to induce Obelix and neither sufficient nor necessary for induction of TrkC. These genes are also not induced by retinoic
The purpose of the study is to measure decline in episodic memory in participants with early AD taking carvedilol compared to placebo treatment as evidenced by the Hopkins Verbal Learning Test (HVLT). cerebrospinal fluid levels of Aβ oligomers in early AD, will be measured in participants receiving carvedilol treatment when compared to placebo treatment. Adverse effects will be monitored in participants receiving carvedilol when compared to placebo.. To assess adverse events, routine chemistry and hematology studies, vital signs, and electrocardiographic parameters before and after 6 months randomized placebo-controlled double-blind treatment with carvedilol at a target dose of 25 mg daily, comparing 25 early AD participants taking carvedilol vs. 25 early AD participants taking placebo. ...
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• Severe hyperkalemia occurred in a patient with radiation pneumonitis and glaucoma shortly after beginning prednisone therapy. There was no evidence of renal f
The 2017 Clay Research Award has been made to Eugenia Malinnikova and Aleksandr Logunov in recognition of their introduction of a novel geometric combinatorial method to study doubling properties of solutions to elliptic eigenvalue problems.. ...
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At optimal dosage levels, combination daily treatment with 2-chloro-4′, 4″-di-2-imidazolin-2-ylterephthalanilide dihydrochloride (NSC-38280) and Methotrexate (MTX) was approximately 100 per cent more effective than the optimal daily dose of either drug alone in increasing the median survival time of mice with advanced leukemia L1210. Maximum antileukemic effectiveness was obtained with the combination of low, relatively ineffective levels of NSC-38280 plus highly effective levels of MTX. At the optimal dosage ratio, administered daily, combination treatment resulted in an increase in the range of doses over which a high level of therapeutic effectiveness was achieved.. The data indicate that the therapeutic synergism resulted from a marked degree of additivity of antitumor activity with only minimal additive toxicity for the host.. ...
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jrepin writes in to recommend a piece by Eugenia from OSNews, which explores the depths of the MPEG-LAs lock on video. One part of the problem is that almost all video cameras, including ones that cost more than $12,000, declare in their manuals that they are for personal use and non-commercial p...
Repeated oral administration of 400 mg/day of ketoconazole, a potent inhibitor of CYP3A4, increased alfuzosin Cmax by 2.3-fold and AUClast by 3.2-fold, following a single 10 mg dose of alfuzosin.. In another study, repeated oral administration of a lower (200 mg/day) dose of ketoconazole increased alfuzosin Cmax by 2.1 -fold and AUClast by 2.5-fold, following a single 10 mg dose of alfuzosin. Therefore, alfuzosin hydrochloride is contraindicated for co-administration with potent inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, or ritonavir) because of increased alfuzosin exposure[ see Contraindications (4), Warnings and Precautions (5.4 ) and Drug Interactions ( 7.1)].. Moderate CYP3A4 Inhibitors Diltiazem: Repeated co-administration of 240 mg/day of diltiazem, a moderately-potent inhibitor of CYP3A4, with 7.5 mg/day (2.5 mg three times daily) alfuzosin (equivalent to the exposure with alfuzosin hydrochloride) increased the Cmax and AUC0-24 of alfuzosin 1.5- and 1.3-fold, respectively. ...
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Orthostatic plasma norepinephrine level as a predictor for therapeutic response to metoprolol in children with postural...  Orthostatic plasma norepinephrine level as a predictor for therapeutic response to metoprolol in children with postural...
Clinical and physiological effects of an acute alpha-1 adrenergic agonist and a beta-1 adrenergic antagonist in chronic ... Convertino VA, Sather TM: Effects of cholinergic and beta-adrenergic blockade on orthostatic tolerance in healthy subjects. ... a logical treatment strategy would be to reduce the HR with β-adrenergic blockade. Raj et al. reported that low-dose oral ... a logical treatment strategy would be reducing the HR with β-adrenergic blockade. β-blockers have been reported to improve ...
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Topical timolol maleate 0.5% for infantile capillary haemangioma of the eyelid. - Nuffield Department of Clinical Neurosciences  Topical timolol maleate 0.5% for infantile capillary haemangioma of the eyelid. - Nuffield Department of Clinical Neurosciences
Adrenergic beta-Antagonists, Eyelid Neoplasms, Hemangioma, Capillary, Humans, Orbital Neoplasms, Propranolol. © 2018 Nuffield ...
more infohttps://www.ndcn.ox.ac.uk/publications/621506
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Hypoglycemia may be difficult to recognize in the elderly, and in people who are taking β-adrenergic blocking drugs. ... Like other calcium channel antagonists, diltiazem decreases sinoatrial and atrioventricular conduction in isolated tissues and ... Effects of alpha- and beta-adrenergic blocking agents on serum prolactin levels in women with hyperprolactinemia and ...
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Effect of Flos carthami Extract and α1-Adrenergic Antagonists on the Porcine Proximal Ureteral Peristalsis  Effect of Flos carthami Extract and α1-Adrenergic Antagonists on the Porcine Proximal Ureteral Peristalsis
... San-Yuan Wu,1,2 Kee ... For example, the variation (SEM) is so high in lower concentration of both data of α-adrenergic antagonists and FC extract. It ... adrenergic antagonists on human ureteral activity [13]. Hernandez et al. investigated ureteral peristalsis in porcine ureter ... adrenoceptor antagonists), and tamsulosin (selective -adrenoceptor antagonist). The tested concentrations of all α-blockers ...
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Adrenergic antagonist - Wikipedia  Adrenergic antagonist - Wikipedia
The α-adrenergic antagonists have different effects from the β-adrenergic antagonists. Adrenergic ligands are endogenous ... While a only a few α-adrenergic antagonists are competitive, all β-adrenergic antagonists are competitive antagonists. ... an α1-adrenergic antagonist will result in vasodilation. Some adrenergic antagonists, mostly β antagonists, passively diffuse ... An adrenergic antagonist is a drug that inhibits the function of adrenergic receptors. There are five adrenergic receptors, ...
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Beta-2 adrenergic antagonist - Wikipedia  Beta-2 adrenergic antagonist - Wikipedia
A Beta-2 adrenergic antagonist (β2-adrenoceptor antagonist) is an adrenergic antagonist which blocks the beta-2 adrenergic ... ICI-118,551 Butaxamine Propranolol Betablocker Beta-2 adrenergic receptor Beta2-adrenergic agonist Bilski, AJ; Halliday, SE; ... an antagonist for β2 and for β1 or β3 adrenoceptors) like the non-selective betablocker Propranolol. ... Fitzgerald, JD; Wale, JL (1983). "The pharmacology of a beta 2-selective adrenoceptor antagonist (ICI 118,551)". J Cardiovasc ...
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Adrenergic Beta-antagonists | Encyclopedia.com  Adrenergic Beta-antagonists | Encyclopedia.com
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Adrenergic beta Antagonists. Drugs that bind to but do not activate beta-Adrenergic Receptors thereby blocking the actions of ... Adrenergic beta-antagonists are used for treatment of Hypertension, Cardiac Arrhythmias, Angina Pectoris, Glaucoma, Migraine ...
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Effects of alpha, beta 1, and beta 2 adrenergic antagonists on...  Effects of alpha, beta 1, and beta 2 adrenergic antagonists on...
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Screening for potential beta 2-adrenergic receptor antagonists using CypHer5E and IN Cell Analyzer 1000 ( 		               ...  Screening for potential beta 2-adrenergic receptor antagonists using CypHer5E and IN Cell Analyzer 1000 ( ...
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  • Here, ex vivo organ bath experiment was further performed to study the effect of FC extract on the inhibition of phenylepinephrine (PE) (10 −4 and 10 −3 M) ureteral peristalsis of porcine ureters with several α 1 -adrenergic antagonists (doxazosin, tamsulosin, and terazosin) as experimental controls. (hindawi.com)
  • Adrenergic ligands are endogenous proteins that modulate and evoke specific cardiovascular effects. (wikipedia.org)
  • Since this response, which is mostly seen as an increase in blood pressure, is produced by the release of the endogenous adrenergic ligands], administration of an adrenergic antagonist results a decrease in blood pressure, which is controlled by both heart rate and vasculature tone. (wikipedia.org)
  • CypHer5E, consequently, can be used to screen for novel antagonists of known receptors and for potential ligands of non-G-protein coupled receptors (5) and orphan receptors. (bio-medicine.org)
  • Perhaps, acceptance and use were facilitated by the sound physiologic and pathophysiologic basis for these findings: that β-adrenergic antagonism (even if partial) decreases myocardial oxygen consumption by decreasing heart rate (and, thus, work) and myocardial contractility, while at the same time increasing diastolic time and coronary artery flow, thus improving the balance of myocardial oxygen delivery and oxygen consumption. (asahq.org)
  • Also, it has been speculated that at least some of the β-adrenergic blockade-induced reduction of myocardial infarction may be due to plaque stabilization, 7 because of hemodynamic-induced plaque stress reduction. (asahq.org)
  • Partial opioid agonist and potent antagonist, is a potent analgesic that can be administered once a day to block withdrawal symptoms. (medscape.com)
  • More recently, a flawed retrospective analysis using propensity score, but with unsuccessful matching, of more than half a million surgical patients in 329 U.S. hospitals noted a decreased mortality for high-risk patients but no improvement of mortality for low-risk patients given β-adrenergic antagonists during the first 2 days of hospitalization. (asahq.org)
  • These antagonists have a been proven to relieve the pain caused by myocardial infarction, and also the infarction size, which correlates with heart rate. (wikipedia.org)