Drugs that bind to and block the activation of PURINERGIC RECEPTORS.
A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
Cell surface proteins that bind PURINES with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized classes of purinergic receptors in mammals are the P1 receptors, which prefer ADENOSINE, and the P2 receptors, which prefer ATP or ADP.
A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.
Compounds that bind to and activate PURINERGIC RECEPTORS.
A subclass of purinergic P2 receptors that signal by means of a ligand-gated ion channel. They are comprised of three P2X subunits which can be identical (homotrimeric form) or dissimilar (heterotrimeric form).
A purinergic P2X neurotransmitter receptor that plays a role in pain sensation signaling and regulation of inflammatory processes.
A subclass of purinergic P2Y receptors that have a preference for ATP and UTP. The activated P2Y2 receptor acts through a G-PROTEIN-coupled PHOSPHATIDYLINOSITOL and intracellular CALCIUM SIGNALING pathway.
A subclass of purinergic P2Y receptors that have a preference for ATP and ADP. The activated P2Y1 receptor signals through the G-PROTEIN-coupled activation of PHOSPHOLIPASE C and mobilization of intracellular CALCIUM.
Compounds that bind to and block the stimulation of PURINERGIC P2X RECEPTORS. Included under this heading are antagonists for specific P2X receptor subtypes.
Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.
A purinergic P2X neurotransmitter receptor involved in sensory signaling of TASTE PERCEPTION, chemoreception, visceral distension, and NEUROPATHIC PAIN. The receptor comprises three P2X3 subunits. The P2X3 subunits are also associated with P2X2 RECEPTOR subunits in a heterotrimeric receptor variant.
Compounds that bind to and stimulate PURINERGIC P2 RECEPTORS.
A widely distributed purinergic P2X receptor subtype that plays a role in pain sensation. P2X4 receptors found on MICROGLIA cells may also play a role in the mediation of allodynia-related NEUROPATHIC PAIN.
Compounds that bind to and stimulate PURINERGIC P2X RECEPTORS. Included under this heading are agonists for specific P2X receptor subtypes.
A subclass of purinergic P2 receptors whose signaling is coupled through a G-PROTEIN signaling mechanism.
A purinergic P2X neurotransmitter receptor involved in sensory signaling of TASTE PERCEPTION, chemoreception, visceral distension and NEUROPATHIC PAIN. The receptor comprises three P2X2 subunits. The P2X2 subunits also have been found associated with P2X3 RECEPTOR subunits in a heterotrimeric receptor variant.
Compounds that bind to and stimulate PURINERGIC P2Y RECEPTORS. Included under this heading are agonists for specific P2Y receptor subtypes.
A purinergic P2X neurotransmitter receptor found at high levels in the BRAIN and IMMUNE SYSTEM.
Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety.
This is the active form of VITAMIN B 6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (PYRIDOXAMINE).
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).
A calcium-activated enzyme that catalyzes the hydrolysis of ATP to yield AMP and orthophosphate. It can also act on ADP and other nucleoside triphosphates and diphosphates. EC 3.6.1.5.
A purinergic P2X neurotransmitter receptor found at sympathetically innervated SMOOTH MUSCLE. It may play a functional role regulating the juxtoglomerular apparatus of the KIDNEY.
Compounds that act on PURINERGIC RECEPTORS or influence the synthesis, storage, uptake, metabolism, or release of purinergic transmitters.
Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.
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.
A subclass of purinergic P2Y receptors that have a preference for ADP binding and are coupled to GTP-BINDING PROTEIN ALPHA SUBUNIT, GI. The P2Y12 purinergic receptors are found in PLATELETS where they play an important role regulating PLATELET ACTIVATION.
Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.
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.
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.
Compounds that bind to and block the stimulation of PURINERGIC P2Y RECEPTORS. Included under this heading are antagonists for specific P2Y receptor subtypes.
Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
Agents inhibiting the effect of narcotics on the central nervous system.
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.

Adenosine 5'-triphosphate and neuropeptide Y are co-transmitters in conjunction with noradrenaline in the human saphenous vein. (1/114)

1. Human saphenous veins were used to assess the cooperative participation of adenosine 5-triphosphate (ATP), neuropeptide Y (NPY), and noradrenaline (NA) in the vasomotor responses elicited following electrical depolarization of the perivascular nerve terminals. Rings from recently dissected human biopsies were mounted to record isometric muscular contractions; the motor activity elicited in the circular muscle layer following electrical depolarization (2.5-20 Hz, 50 V, 0.5 msec) were recorded. 2. Incubation of the biopsies with either 100 nM tetrodotoxin (TTX) or 1 microM guanethidine abolished the vasomotor response elicited by electrical nerve depolarization. The independent application of either ATP or NA to vein rings induced concentration-dependent contractions. 3. Tissue incubation with 30 microM suramin or 10 nM prazosin produced 10 fold rightward displacements of the alpha,beta-methylene ATP and NA concentration-response curves respectively. NPY contracted a limited number of biopsies, the vasoconstriction elicited was completely blocked by 1 microM BIBP 3226. A 5 min incubation of the biopsies with 10-100 nM NPY synergized, in a concentration-dependent fashion, both the ATP and the ATP analogue-induced contractions. Likewise, tissue preincubation with 10 nM NPY potentiated the vasomotor responses evoked with 20-60 nM NA. 4. Neither suramin, BIBP 3226, nor prazosin was individually able to significantly modify the derived frequency-tension curves. In contrast, the co-application of 30 microM suramin and 10 nM prazosin or 30 microM suramin and 1 microM BIBP 3226, elicited a significant (P<0.01) downward displacement of the respective frequency-tension curves. 5. The simultaneous application of the three antagonists-30 microM suramin, 1 microM BIBP 3226 and 10 nM prazosin-caused a significantly greater displacement of the frequency-tension curve than that achieved in experiments using two of these antagonists. 6. Electrically-evoked vasomotor activity is blocked to a larger extent by tissue incubation with 2.5 microM chloroethylclonidine and 30 microM suramin rather than with 10 nM 5 methyl urapidil and 30 microM suramin. As a result, the alpha1-adrenoceptor involved in the vasomotor activity has tentatively been associated with the alpha1B adrenoceptor family subtype. 7. Results support the physiological role of ATP in sympathetic neurotransmission. The present results are consistent with the working hypothesis that human sympathetic vasomotor reflexes involve the coordinated motor action of ATP, NPY, and NA acting on vascular smooth muscle cells. The present results support the concept of sympathetic co-transmission in the human saphenous vein.  (+info)

Adrenergic and purinergic components in bisected vas deferens from spontaneously hypertensive rats. (2/114)

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)

Effects of prolonged cold storage on purinergic and adrenergic components of sympathetic co-transmission in isolated canine splenic arteries. (3/114)

The present study demonstrated the progressive inhibition by prolonged cold storage (4, 7 and 14 days at 4 degrees C) on prejunctional and postjunctional functions of purinergic and adrenergic components of double-peaked vasoconstrictor responses to periarterial electrical nerve stimulation in the isolated canine splenic artery. After the cold storage for 4 days, the first phase constriction was markedly decreased, whereas the second response was not significantly modified. Furthermore, after the 7 days of cold storage, the first phase was substantially depressed at low frequencies, but at high frequencies, a low level of contractile responses was still observed. On the other hand, the second phase in the cold stored artery for 7 days largely remained at any used frequencies. Moreover, the 14 days of cold storage almost completely inhibited the vasoconstrictor responses to nerve stimulation. Tyramine-induced constrictions were progressively decreased in the stored-days dependent manner, although the ATP and the noradrenaline-induced one was not modified for 4 and 7 days of the cold storage. In conclusion, 1) the 4 degrees C cold stored artery for 4 days may show preferential injury of its tyramine-dependent noradrenaline releasing mechanisms, whereas nerve excited ones might well remain; and 2) the prejunctional contractile response of purinergic transmission might be damaged more preferentially than that of adrenergic transmission within 7 days storage.  (+info)

Purinergic and cholinergic neuro-neuronal transmission underlying reflexes activated by mucosal stimulation in the isolated guinea-pig ileum. (4/114)

1. We present evidence that adenosine triphosphate (ATP) plays a major role in excitatory neuro-neuronal transmission in ascending and descending reflex pathways to the longitudinal (LM) and circular muscle (CM). 2. A partitioned bath was used for the pharmacological isolation of a segment of guinea-pig ileum ( approximately 6 cm in length), allowing drugs to be selectively applied to an intermediate region between the region where mucosal stimulation was applied and that where mechanical recordings were made. 3. Brush stroking the mucosa (3 strokes) elicited a synchronous contraction of the LM and CM both above (ascending excitation) and below (descending excitation) the site of stimulation. All reflexes were abolished when tetrodotoxin (1 microM) was applied to the intermediate chamber. 4. Hexamethonium (300 microM) added to the intermediate chamber abolished the ascending contraction in 15 % of oral preparations (from 26 preparations, 18 animals) and the descending contraction in 13% of anal preparations studied (from 53 preparations, 48 animals). In the remaining 85% of oral preparations, hexamethonium usually attenuated the oral contraction of the LM and CM. However, in the remaining 87% of anal preparations, hexamethonium had no effect on the anal contraction of the LM and CM. 5. Oral and anal reflexes that were hexamethonium resistant were either abolished or attenuated by the further addition of the P2 purinergic receptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 10 microM) or alpha,beta-methylene ATP (50-100 microM) to the intermediate chamber. 6. 1,1-Dimethyl-4-phenyl-piperazinium iodide (DMPP, 20 microM) or alpha,beta-methylene ATP (50-100 microM) stimulated both ascending and descending excitatory pathways, when applied to the intermediate chamber. 7. In conclusion, ascending and descending neuro-neuronal transmission in excitatory nervous pathways to the LM and CM is complex and clearly involves neurotransmitter(s) other than acetylcholine (ACh). We suggest mucosal stimulation releases ACh and ATP in both ascending and descending excitatory reflex pathways that synapse with excitatory motoneurons to the LM and CM.  (+info)

ATP-mediated glia signaling. (5/114)

Glia calcium signaling has recently been identified as a potent modulator of synaptic transmission. We show here that the spatial expansion of calcium waves is mediated by ATP and subsequent activation of purinergic receptors. Ectopic expression of gap junction proteins, connexins (Cxs), leads to an increase in both ATP release and the radius of calcium wave propagation. Cx expression was also associated with a phenotypic transformation, and cortical neurons extended longer neurites when co-cultured with Cx-expressing than with Cx-deficient cells. Purinergic receptor activation mediated both these effects, because treatment with receptor antagonists restored the glia phenotype and slowed neurite outgrowth. These results identify a key role of ATP in both short-term calcium signaling events and in long-term differentiation regulated by glia.  (+info)

Cardiovascular and pulmonary response to oral administration of ATP in rabbits. (6/114)

Extracellular purines such as ATP and adenosine participate in the regulation of cardiovascular and respiratory functions through specific P1 and P2 purine receptors. These properties have mainly been described after intravenous infusion. Experiments reported herein were designed to explore the possible effect of oral ATP administration (3 or 20 mg. kg(-1). day(-1)) on vascular, cardiac, and pulmonary functions in rabbits. Whereas a unique oral dose of ATP has no effect, chronic supplementation during 14 days reduces peripheral vascular resistance, pulmonary resistance, and respiratory frequency and increases arterial PO(2). No effect on central blood pressure and heart rate is observed, but an increase of the left ventricular work index is noticed subsequent to the diminution of vascular resistance. Rather similar cardiovascular modifications are observed in rabbits given 20 mg. kg(-1). day(-1) adenosine for 14 days but without variation of respiratory parameters. These original effects of repeated oral treatment with ATP may result from an adaptive metabolic response to nucleoside supplementation that might affect the turnover of extracellular purines leading to P1- and/or P2-receptor activation.  (+info)

Tamoxifen-induced enhancement of calcium signaling in glioma and MCF-7 breast cancer cells. (7/114)

The antiestrogen tamoxifen is commonly used to treat breast cancer, but it also has therapeutic activity in several other types of cancer. Many of these tumors, including malignant gliomas, are estrogen receptor negative. Nonetheless, high concentrations of tamoxifen can directly reduce cell proliferation in some of these tumors and induce apoptosis. In this study, the role of tamoxifen in calcium signaling and calcium-induced cell death was studied in both malignant glioma cell lines and MCF-7 breast cancer cells. Tamoxifen potently increased the spatial expansion of calcium waves by 30-150% while significantly enhancing and prolonging agonist-induced calcium elevations. Furthermore, tamoxifen pretreatment accelerated calcium ionophore-induced death by more than 20 min, suggesting that tamoxifen lowered cellular resistance to calcium loads. In contrast to its potentiating of calcium signaling in tumors, tamoxifen had no significant effect on calcium signaling in cultures of primary astrocytes from either human or rat brain. This study demonstrates the existence of calcium signaling in breast cancer and glioma cells and identifies tamoxifen as a potential modulator of tumor-associated calcium signaling.  (+info)

Adenosine- and adenine-nucleotide-mediated inhibition of normal and transformed keratinocyte proliferation is dependent upon dipyridamole-sensitive adenosine transport. (8/114)

Extracellular adenosine and its related nucleotides have been referred to as retaliatory metabolites that can be released into the extracellular environment during inflammation, wounding, and other pathologic states. We have previously reported that these compounds reversibly inhibit the proliferation of normal keratinocyte cultures and we now demonstrate that these compounds also arrest the proliferation of transformed keratinocytes. Although our study shows that keratinocytes express mRNA corresponding to the A2B purinoreceptors and that adenosine or AMP treatment elevates intracellular cAMP in these cells, our study also demonstrates that dipyridamole-inhibitable transport of adenosine into the keratinocyte is central to the mechanism by which adenosine and adenine nucleotides arrest proliferation in these cells. In support of this mechanism, our results demonstrate that human keratinocytes express mRNA corresponding to the recently cloned dipyridamole-sensitive human equilibrative nucleoside transporter. Interestingly, coincubation with adenosine deaminase reverses the antiproliferative action of adenosine and exerts no effect on the antiproliferative activity of the adenine nucleotides, thus supporting a model in which adenine nucleotides are enzymatically converted to adenosine and transported into the keratinocyte in a tightly coupled and adenosine-deaminase-resistant manner. Analysis of adenosine- and adenosine-monophosphate-treated keratinocytes demonstrated that quiescence is induced within 12-24 h, and fluorescence-activated cell sorter analysis suggests that treatment with these compounds may result in the inhibition of keratinocyte proliferation at both G1 and S phases of the cell cycle. In addition to their documented antiproliferative action on other cell types, adenosine, adenine nucleotides, and related analogs may also represent a potential new class of pharmacologic regulators of keratinocyte proliferation in vivo.  (+info)

Purinergic antagonists are a class of drugs that block the action of purinergic receptors, which are specialized proteins found on the surface of cells that respond to purines such as ATP and ADP. These receptors play important roles in various physiological processes, including neurotransmission, inflammation, and cell death.

Purinergic antagonists work by binding to these receptors and preventing them from being activated by purines. This can have a variety of effects depending on the specific receptor that is blocked. For example, some purinergic antagonists are used in the treatment of conditions such as chronic pain, depression, and Parkinson's disease because they block receptors that play a role in these conditions.

It's important to note that while purinergic antagonists can be useful therapeutically, they can also have side effects and potential risks. As with any medication, it's important to use them only under the guidance of a healthcare professional.

Suramin is a medication that has been used for the treatment of African sleeping sickness, which is caused by trypanosomes. It works as a reverse-specific protein kinase CK inhibitor and also blocks the attachment of the parasite to the host cells. Suramin is not absorbed well from the gastrointestinal tract and is administered intravenously.

It should be noted that Suramin is an experimental treatment for other conditions such as cancer, neurodegenerative diseases, viral infections and autoimmune diseases, but it's still under investigation and has not been approved by FDA for those uses.

Adenosine Triphosphate (ATP) is a high-energy molecule that stores and transports energy within cells. It is the main source of energy for most cellular processes, including muscle contraction, nerve impulse transmission, and protein synthesis. ATP is composed of a base (adenine), a sugar (ribose), and three phosphate groups. The bonds between these phosphate groups contain a significant amount of energy, which can be released when the bond between the second and third phosphate group is broken, resulting in the formation of adenosine diphosphate (ADP) and inorganic phosphate. This process is known as hydrolysis and can be catalyzed by various enzymes to drive a wide range of cellular functions. ATP can also be regenerated from ADP through various metabolic pathways, such as oxidative phosphorylation or substrate-level phosphorylation, allowing for the continuous supply of energy to cells.

Purinergic receptors are a type of cell surface receptor that bind and respond to purines and pyrimidines, which are nucleotides and nucleosides. These receptors are involved in various physiological processes, including neurotransmission, muscle contraction, and inflammation. There are two main types of purinergic receptors: P1 receptors, which are activated by adenosine, and P2 receptors, which are activated by ATP and other nucleotides.

P2 receptors are further divided into two subtypes: P2X and P2Y. P2X receptors are ionotropic receptors that form cation channels upon activation, allowing the flow of ions such as calcium and sodium into the cell. P2Y receptors, on the other hand, are metabotropic receptors that activate G proteins upon activation, leading to the activation or inhibition of various intracellular signaling pathways.

Purinergic receptors have been found to play a role in many diseases and conditions, including neurological disorders, cardiovascular disease, and cancer. They are also being studied as potential targets for drug development.

Purinergic P2 receptors are a type of cell surface receptor that bind to purine nucleotides and nucleosides, such as ATP (adenosine triphosphate) and ADP (adenosine diphosphate), and mediate various physiological responses. These receptors are divided into two main families: P2X and P2Y.

P2X receptors are ionotropic receptors, meaning they form ion channels that allow the flow of ions across the cell membrane upon activation. There are seven subtypes of P2X receptors (P2X1-7), each with distinct functional and pharmacological properties.

P2Y receptors, on the other hand, are metabotropic receptors, meaning they activate intracellular signaling pathways through G proteins. There are eight subtypes of P2Y receptors (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14), each with different G protein coupling specificities and downstream signaling pathways.

Purinergic P2 receptors are widely expressed in various tissues, including the nervous system, cardiovascular system, respiratory system, gastrointestinal tract, and immune system. They play important roles in regulating physiological functions such as neurotransmission, vasodilation, platelet aggregation, smooth muscle contraction, and inflammation. Dysregulation of purinergic P2 receptors has been implicated in various pathological conditions, including pain, ischemia, hypertension, atherosclerosis, and cancer.

Purinergic agonists are substances that bind to and activate purinergic receptors, which are a type of cell surface receptor found in many tissues throughout the body. These receptors are activated by endogenous molecules called purines, including adenosine triphosphate (ATP) and uridine triphosphate (UTP), as well as their breakdown products such as adenosine.

Purinergic agonists can have a variety of effects on different tissues, depending on the type of purinergic receptor that they activate. For example, ATP acting as a purinergic agonist can cause smooth muscle contraction, increase heart rate and blood pressure, and modulate neurotransmission in the brain.

Purinergic agonists are used in research to study the functions of purinergic receptors and their roles in various physiological processes. They also have potential therapeutic applications, such as in the treatment of cardiovascular diseases, pain, and neurological disorders. However, it is important to note that the use of purinergic agonists as drugs must be carefully studied and regulated due to their potential for adverse effects.

Purinergic P2X receptors are a type of ligand-gated ion channel that are activated by the binding of extracellular ATP (adenosine triphosphate) and other purinergic agonists. These receptors play important roles in various physiological processes, including neurotransmission, pain perception, and immune response.

P2X receptors are composed of three subunits that form a functional ion channel. There are seven different subunits (P2X1-7) that can assemble to form homo- or heterotrimeric receptor complexes with distinct functional properties.

Upon activation by ATP, P2X receptors undergo conformational changes that allow for the flow of cations, such as calcium (Ca^2+^), sodium (Na^+^), and potassium (K^+^) ions, across the cell membrane. This ion flux can lead to a variety of downstream signaling events, including the activation of second messenger systems and changes in gene expression.

Purinergic P2X receptors have been implicated in a number of pathological conditions, including chronic pain, inflammation, and neurodegenerative diseases. As such, they are an active area of research for the development of novel therapeutic strategies.

Purinergic P2X7 receptors are a type of ligand-gated ion channel that are activated by the binding of extracellular adenosine triphosphate (ATP) to the P2X7 receptor subunit. These receptors play important roles in various physiological and pathophysiological processes, including inflammation, immune response, pain perception, and cell death.

Upon activation of P2X7 receptors, there is an increase in membrane permeability to small cations such as Na+, K+, and Ca2+, which can lead to the depolarization of the cell membrane. Prolonged activation of these receptors can result in the formation of large pores that allow for the passage of larger molecules, including inflammatory mediators and even small proteins. This can ultimately lead to the induction of apoptosis or necrosis in certain cells.

P2X7 receptors are widely expressed in various tissues, including the brain, spinal cord, immune cells, and epithelial cells. In recent years, there has been growing interest in targeting P2X7 receptors for therapeutic purposes, particularly in the context of inflammatory diseases and chronic pain.

Purinergic P2Y2 receptors are a type of G-protein coupled receptor (GPCR) that bind to and are activated by extracellular nucleotides, such as ATP and UTP. These receptors play a role in various physiological processes, including regulation of inflammation, smooth muscle contraction, and wound healing.

P2Y2 receptors are widely expressed in various tissues, including the respiratory, gastrointestinal, and urinary tracts, as well as the skin and central nervous system. They have been shown to play a role in the pathophysiology of several diseases, such as cystic fibrosis, asthma, and cancer.

Activation of P2Y2 receptors leads to a variety of cellular responses, including increased intracellular calcium levels, activation of protein kinases, and regulation of gene expression. These downstream signaling events can ultimately lead to changes in cell behavior, such as increased proliferation, migration, or secretion of cytokines and other mediators.

In summary, Purinergic P2Y2 receptors are a type of GPCR that bind to extracellular nucleotides and play a role in various physiological processes and diseases. Activation of these receptors leads to downstream signaling events that can ultimately affect cell behavior.

Purinergic P2Y1 receptors are a type of G-protein coupled receptor (GPCR) that bind to purine nucleotides, such as adenosine triphosphate (ATP) and adenosine diphosphate (ADP). These receptors play a role in various physiological processes, including platelet activation, smooth muscle contraction, and neurotransmission.

The P2Y1 receptor, in particular, is activated by ADP and has been shown to be involved in platelet aggregation, vascular smooth muscle contraction, and neuronal excitability. It signals through the Gq/11 family of G proteins, leading to the activation of phospholipase C-β (PLC-β) and the production of inositol trisphosphate (IP3) and diacylglycerol (DAG), which ultimately result in calcium mobilization and protein kinase C (PKC) activation.

In a medical context, P2Y1 receptors have been implicated in various pathological conditions, including thrombosis, hypertension, and neurodegenerative disorders. Therefore, drugs that target these receptors may have therapeutic potential for the treatment of these conditions.

Purinergic P2X receptor antagonists are pharmaceutical agents that block the activation of P2X receptors, which are ligand-gated ion channels found in the cell membranes of various cell types, including excitable cells such as neurons and muscle cells. These receptors are activated by extracellular adenosine triphosphate (ATP) and play important roles in a variety of physiological processes, including neurotransmission, pain perception, and inflammation.

P2X receptor antagonists work by binding to the receptor and preventing ATP from activating it, thereby blocking its downstream effects. These drugs have potential therapeutic uses in various medical conditions, such as chronic pain, urinary incontinence, and ischemia-reperfusion injury. However, their development and use are still in the early stages of research, and more studies are needed to fully understand their mechanisms of action and safety profiles.

Purinergic P2 receptor antagonists are pharmaceutical agents that block the activity of P2 receptors, which are a type of cell surface receptor that binds extracellular nucleotides such as ATP and ADP. These receptors play important roles in various physiological processes, including neurotransmission, inflammation, and platelet aggregation.

P2 receptors are divided into two main subfamilies: P2X and P2Y. The P2X receptors are ligand-gated ion channels that allow the flow of ions across the cell membrane upon activation, while the P2Y receptors are G protein-coupled receptors that activate intracellular signaling pathways.

Purinergic P2 receptor antagonists are used in clinical medicine to treat various conditions, such as chronic pain, urinary incontinence, and cardiovascular diseases. For example, the P2X3 receptor antagonist gefapixant is being investigated for the treatment of refractory chronic cough, while the P2Y12 receptor antagonists clopidogrel and ticagrelor are used to prevent thrombosis in patients with acute coronary syndrome.

Overall, purinergic P2 receptor antagonists offer a promising therapeutic approach for various diseases by targeting specific receptors involved in pathological processes.

Purinergic P2X3 receptors are a type of ligand-gated ion channel that are activated by the binding of adenosine triphosphate (ATP) and related nucleotides. These receptors are primarily expressed on sensory neurons, including nociceptive neurons that detect and transmit pain signals.

P2X3 receptors are homomeric or heteromeric complexes composed of P2X3 subunits, which form a functional ion channel upon activation by ATP. These receptors play an important role in the transmission of nociceptive information from the periphery to the central nervous system.

Activation of P2X3 receptors leads to the opening of the ion channel and the influx of cations, such as calcium and sodium ions, into the neuron. This depolarizes the membrane and can trigger action potentials that transmit pain signals to the brain.

P2X3 receptors have been implicated in various pain conditions, including inflammatory pain, neuropathic pain, and cancer-related pain. As a result, P2X3 receptor antagonists are being investigated as potential therapeutic agents for the treatment of chronic pain.

Purinergic P2 receptor agonists are substances that bind and activate purinergic P2 receptors, which are a type of cell surface receptor found in many tissues throughout the body. These receptors are activated by extracellular nucleotides, such as ATP (adenosine triphosphate) and ADP (adenosine diphosphate), and play important roles in various physiological processes, including neurotransmission, muscle contraction, and inflammation.

P2 receptors are divided into two main subfamilies: P2X and P2Y. P2X receptors are ligand-gated ion channels that allow the flow of ions across the cell membrane when activated, while P2Y receptors are G protein-coupled receptors that activate intracellular signaling pathways.

Purinergic P2 receptor agonists can be synthetic or naturally occurring compounds that selectively bind to and activate specific subtypes of P2 receptors. They have potential therapeutic applications in various medical conditions, such as pain management, cardiovascular diseases, and neurological disorders. However, their use must be carefully monitored due to the potential for adverse effects, including desensitization of receptors and activation of unwanted signaling pathways.

Purinergic P2X4 receptors are a type of ionotropic purinergic receptor that are activated by adenosine triphosphate (ATP) and related nucleotides. They belong to the P2X receptor family, which includes seven subtypes (P2X1-7) that form trimeric channels permeable to cations such as calcium, sodium, and potassium.

The P2X4 receptor is widely expressed in various tissues, including the central and peripheral nervous systems, immune cells, and epithelial cells. It plays a role in several physiological processes, including neurotransmission, inflammation, and pain perception. Activation of P2X4 receptors leads to an increase in intracellular calcium concentration and membrane depolarization, which can modulate synaptic transmission and cell excitability.

P2X4 receptors have also been implicated in various pathological conditions, such as neuropathic pain, neuroinflammation, and ischemic injury. They are involved in the release of pro-inflammatory cytokines and chemokines from immune cells, contributing to the development of chronic inflammation and tissue damage.

In summary, purinergic P2X4 receptors are a type of ATP-gated ion channel that play important roles in physiological and pathological processes, including neurotransmission, inflammation, and pain perception.

Purinergic P2X receptors are a type of ionotropic receptor, which are ligand-gated ion channels that open to allow ions to flow across the cell membrane in response to the binding of a neurotransmitter or other signaling molecule. Specifically, purinergic P2X receptors are activated by extracellular adenosine triphosphate (ATP) and related nucleotides.

Agonists of purinergic P2X receptors are substances that bind to and activate these receptors, causing them to open and allow ions to flow through. Examples of natural agonists of purinergic P2X receptors include ATP, adenosine diphosphate (ADP), and uridine triphosphate (UTP). There are also synthetic agonists that have been developed for research purposes, such as α,β-methylene ATP and benzoylbenzoyl ATP.

Agonists of purinergic P2X receptors have a variety of effects on different cell types, depending on the specific receptor subtype that is activated. For example, activation of P2X1 receptors on smooth muscle cells can cause contraction, while activation of P2X7 receptors on immune cells can trigger the release of pro-inflammatory cytokines.

Understanding the effects of purinergic P2X receptor agonists is important for a variety of research areas, including neuroscience, immunology, and cardiovascular biology. It may also have implications for the development of new therapeutic strategies for various diseases.

Purinergic P2Y receptors are a subtype of purinergic receptors that are activated by nucleotides, such as ATP (adenosine triphosphate), ADP (adenosine diphosphate), UTP (uridine triphosphate), and UDP (uridine diphosphate). These receptors are G protein-coupled receptors, which means they transmit signals through heterotrimeric G proteins.

There are eight subtypes of P2Y receptors, named P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14. Each subtype has a different preference for the type of nucleotide that activates it, as well as distinct downstream signaling pathways.

P2Y receptors play important roles in various physiological processes, including platelet aggregation, smooth muscle contraction and relaxation, neurotransmission, inflammation, and cell proliferation and differentiation. In the medical field, P2Y receptors have been implicated in several diseases, such as thrombosis, hypertension, chronic pain, and cancer, making them potential targets for drug development.

Purinergic P2X2 receptors are a type of ionotropic receptor, which are ligand-gated ion channels that open to allow the flow of ions across the cell membrane in response to the binding of a specific molecule (ligand). In the case of P2X2 receptors, the ligands are ATP and other purinergic agonists.

P2X2 receptors are composed of three subunits that assemble to form a functional ion channel. When ATP binds to the extracellular domain of the receptor, it triggers a conformational change that opens the channel, allowing cations such as calcium (Ca²+), sodium (Na⁺) and potassium (K⁺) to flow into the cell.

P2X2 receptors are widely expressed in both the peripheral and central nervous systems, where they play important roles in various physiological processes, including neurotransmission, pain perception, and vasoconstriction. They have also been implicated in several pathological conditions, such as chronic pain, epilepsy, and bladder dysfunction.

P2X2 receptors are of particular interest in pharmacology due to their potential as targets for drug development. For example, P2X2 receptor antagonists have been shown to be effective in reducing pain hypersensitivity in animal models of chronic pain.

Purinergic P2Y receptor agonists are substances that bind and activate purinergic P2Y receptors, which are a type of G-protein coupled receptors found on the cell membrane. These receptors are activated by extracellular nucleotides such as ATP (adenosine triphosphate), ADP (adenosine diphosphate), UTP (uridine triphosphate) and UDP (uridine diphosphate).

When a purinergic P2Y receptor agonist binds to the receptor, it triggers a series of intracellular signaling events that can lead to various cellular responses, such as modulation of neurotransmission, regulation of vascular tone, and activation of immune cells.

Purinergic P2Y receptor agonists have potential therapeutic applications in several medical conditions, including cardiovascular diseases, inflammatory disorders, and neurological disorders. However, the use of these agents must be carefully monitored due to their potential to cause adverse effects, such as vasoconstriction, platelet aggregation, and inflammation.

Purinergic P2X5 receptors are a type of ionotropic purinergic receptor that are activated by adenosine triphosphate (ATP) and related nucleotides. They belong to the P2X receptor family, which includes seven subtypes (P2X1-7) that form trimeric channels permeable to cations such as calcium, sodium, and potassium.

The P2X5 receptor is composed of three identical subunits that contain two transmembrane domains, an intracellular N-terminus, and a large extracellular loop with conserved amino acid residues involved in ATP binding. The activation of P2X5 receptors leads to the opening of the ion channel, resulting in membrane depolarization and the initiation of downstream signaling pathways.

P2X5 receptors are widely expressed in various tissues, including the nervous system, immune system, and cardiovascular system. In the nervous system, they play important roles in pain sensation, neuroinflammation, and synaptic plasticity. In the immune system, P2X5 receptors regulate the activation and migration of immune cells, such as macrophages and dendritic cells. In the cardiovascular system, they contribute to the regulation of vascular tone and blood pressure.

Dysregulation of P2X5 receptor function has been implicated in various pathological conditions, including chronic pain, neurodegenerative diseases, and inflammatory disorders. Therefore, targeting P2X5 receptors represents a promising therapeutic strategy for the treatment of these conditions.

Uridine Triphosphate (UTP) is a nucleotide that plays a crucial role in the synthesis and repair of DNA and RNA. It consists of a nitrogenous base called uracil, a pentose sugar (ribose), and three phosphate groups. UTP is one of the four triphosphates used in the biosynthesis of RNA during transcription, where it donates its uracil base to the growing RNA chain. Additionally, UTP serves as an energy source and a substrate in various biochemical reactions within the cell, including phosphorylation processes and the synthesis of glycogen and other molecules.

Pyridoxal phosphate (PLP) is the active form of vitamin B6 and functions as a cofactor in various enzymatic reactions in the human body. It plays a crucial role in the metabolism of amino acids, carbohydrates, lipids, and neurotransmitters. Pyridoxal phosphate is involved in more than 140 different enzyme-catalyzed reactions, making it one of the most versatile cofactors in human biochemistry.

As a cofactor, pyridoxal phosphate helps enzymes carry out their functions by facilitating chemical transformations in substrates (the molecules on which enzymes act). In particular, PLP is essential for transamination, decarboxylation, racemization, and elimination reactions involving amino acids. These processes are vital for the synthesis and degradation of amino acids, neurotransmitters, hemoglobin, and other crucial molecules in the body.

Pyridoxal phosphate is formed from the conversion of pyridoxal (a form of vitamin B6) by the enzyme pyridoxal kinase, using ATP as a phosphate donor. The human body obtains vitamin B6 through dietary sources such as whole grains, legumes, vegetables, nuts, and animal products like poultry, fish, and pork. It is essential to maintain adequate levels of pyridoxal phosphate for optimal enzymatic function and overall health.

Purinergic P1 receptors are a type of G-protein coupled receptor that bind to nucleotides such as adenosine. These receptors are involved in a variety of physiological processes, including modulation of neurotransmitter release, cardiovascular function, and immune response. There are four subtypes of P1 receptors (A1, A2A, A2B, and A3) that have different signaling pathways and functions. Activation of these receptors can lead to a variety of cellular responses, including inhibition or stimulation of adenylyl cyclase activity, changes in intracellular calcium levels, and activation of various protein kinases. They play important roles in the central nervous system, cardiovascular system, respiratory system, gastrointestinal system, and immune system.

Apyrase is an enzyme that catalyzes the hydrolysis of nucleoside triphosphates (like ATP or GTP) to nucleoside diphosphates (like ADP or GDP), releasing inorganic phosphate in the process. It can also hydrolyze nucleoside diphosphates to nucleoside monophosphates, releasing inorganic pyrophosphate.

This enzyme is widely distributed in nature and has been found in various organisms, including bacteria, plants, and animals. In humans, apyrases are present in different tissues, such as the brain, platelets, and red blood cells. They play essential roles in several biological processes, including signal transduction, metabolism regulation, and inflammatory response modulation.

There are two major classes of apyrases: type I (also known as nucleoside diphosphate kinase) and type II (also known as NTPDase). Type II apyrases have higher substrate specificity for nucleoside triphosphates, while type I apyrases can hydrolyze both nucleoside tri- and diphosphates.

In the medical field, apyrases are sometimes used in research to study platelet function or neurotransmission, as they can help regulate purinergic signaling by controlling extracellular levels of ATP and ADP. Additionally, some studies suggest that apyrase activity might be involved in certain pathological conditions, such as atherosclerosis, thrombosis, and neurological disorders.

Purinergic P2X1 receptors are a type of ligand-gated ion channel that is activated by the binding of ATP (adenosine triphosphate), a purine nucleotide. These receptors are permeable to cations such as calcium, sodium, and potassium ions. P2X1 receptors are widely expressed in various tissues, including the cardiovascular system, nervous system, and urinary system. They play a role in several physiological processes, including neurotransmission, smooth muscle contraction, and platelet aggregation.

P2X1 receptors are composed of three subunits that form a homotrimeric complex. Upon activation by ATP, the channel opens, allowing cations to flow through the membrane. This ion flux can trigger various intracellular signaling pathways and modulate cellular functions.

In summary, Purinergic P2X1 receptors are a type of ATP-activated ion channel that play important roles in several physiological processes and are widely expressed in various tissues throughout the body.

Purinergic agents are substances that act on purinergic receptors, which are a type of cell surface receptor found in many organs and tissues throughout the body. These receptors are activated by endogenous molecules called purines, including adenosine triphosphate (ATP) and adenosine diphosphate (ADP), as well as uridine triphosphate (UTP) and other related compounds.

Purinergic agents can be either agonists or antagonists of purinergic receptors. Agonists are molecules that bind to the receptor and activate it, leading to a physiological response. Antagonists, on the other hand, bind to the receptor but do not activate it, instead blocking the ability of agonists to bind and activate the receptor.

Purinergic agents have a wide range of therapeutic applications, including in the treatment of cardiovascular diseases, neurological disorders, inflammatory conditions, and pain management. For example, certain purinergic agonists can be used to induce vasodilation and improve blood flow, while antagonists may be useful in treating conditions such as chronic pain or epilepsy.

It's worth noting that the study of purinergic signaling is a rapidly evolving field, and new insights into the roles of purinergic agents in various physiological processes are being discovered regularly.

Purinergic P1 receptor antagonists are a class of pharmaceutical drugs that block the activity of purinergic P1 receptors, which are a type of G-protein coupled receptor found in many tissues throughout the body. These receptors are activated by extracellular nucleotides such as adenosine and ATP, and play important roles in regulating a variety of physiological processes, including cardiovascular function, neurotransmission, and immune response.

Purinergic P1 receptor antagonists work by binding to these receptors and preventing them from being activated by nucleotides. This can have various therapeutic effects, depending on the specific receptor subtype that is targeted. For example, A1 receptor antagonists have been shown to improve cardiac function in heart failure, while A2A receptor antagonists have potential as anti-inflammatory and neuroprotective agents.

However, it's important to note that the use of purinergic P1 receptor antagonists is still an area of active research, and more studies are needed to fully understand their mechanisms of action and therapeutic potential.

Hormone antagonists are substances or drugs that block the action of hormones by binding to their receptors without activating them, thereby preventing the hormones from exerting their effects. They can be classified into two types: receptor antagonists and enzyme inhibitors. Receptor antagonists bind directly to hormone receptors and prevent the hormone from binding, while enzyme inhibitors block the production or breakdown of hormones by inhibiting specific enzymes involved in their metabolism. Hormone antagonists are used in the treatment of various medical conditions, such as cancer, hormonal disorders, and cardiovascular diseases.

Purinergic P2Y12 receptors are a type of G protein-coupled receptor that bind to and are activated by adenosine diphosphate (ADP). These receptors play an important role in regulating platelet activation and aggregation, which is crucial for the normal hemostatic response to vascular injury.

The P2Y12 receptor is a key component of the platelet signaling pathway that leads to the activation of integrin αIIbβ3, which mediates platelet aggregation. Inhibition of the P2Y12 receptor with drugs such as clopidogrel or ticagrelor is a standard treatment for preventing thrombosis in patients at risk of arterial occlusion, such as those with acute coronary syndrome or following percutaneous coronary intervention.

P2Y12 receptors are also expressed on other cell types, including immune cells and neurons, where they play roles in inflammation, neurotransmission, and other physiological processes.

Excitatory amino acid antagonists are a class of drugs that block the action of excitatory neurotransmitters, particularly glutamate and aspartate, in the brain. These drugs work by binding to and blocking the receptors for these neurotransmitters, thereby reducing their ability to stimulate neurons and produce an excitatory response.

Excitatory amino acid antagonists have been studied for their potential therapeutic benefits in a variety of neurological conditions, including stroke, epilepsy, traumatic brain injury, and neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. However, their use is limited by the fact that blocking excitatory neurotransmission can also have negative effects on cognitive function and memory.

There are several types of excitatory amino acid receptors, including N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainite receptors. Different excitatory amino acid antagonists may target one or more of these receptor subtypes, depending on their specific mechanism of action.

Examples of excitatory amino acid antagonists include ketamine, memantine, and dextromethorphan. These drugs have been used in clinical practice for various indications, such as anesthesia, sedation, and treatment of neurological disorders. However, their use must be carefully monitored due to potential side effects and risks associated with blocking excitatory neurotransmission.

Sprague-Dawley rats are a strain of albino laboratory rats that are widely used in scientific research. They were first developed by researchers H.H. Sprague and R.C. Dawley in the early 20th century, and have since become one of the most commonly used rat strains in biomedical research due to their relatively large size, ease of handling, and consistent genetic background.

Sprague-Dawley rats are outbred, which means that they are genetically diverse and do not suffer from the same limitations as inbred strains, which can have reduced fertility and increased susceptibility to certain diseases. They are also characterized by their docile nature and low levels of aggression, making them easier to handle and study than some other rat strains.

These rats are used in a wide variety of research areas, including toxicology, pharmacology, nutrition, cancer, and behavioral studies. Because they are genetically diverse, Sprague-Dawley rats can be used to model a range of human diseases and conditions, making them an important tool in the development of new drugs and therapies.

Dopamine antagonists are a class of drugs that block the action of dopamine, a neurotransmitter in the brain associated with various functions including movement, motivation, and emotion. These drugs work by binding to dopamine receptors and preventing dopamine from attaching to them, which can help to reduce the symptoms of certain medical conditions such as schizophrenia, bipolar disorder, and gastroesophageal reflux disease (GERD).

There are several types of dopamine antagonists, including:

1. Typical antipsychotics: These drugs are primarily used to treat psychosis, including schizophrenia and delusional disorders. Examples include haloperidol, chlorpromazine, and fluphenazine.
2. Atypical antipsychotics: These drugs are also used to treat psychosis but have fewer side effects than typical antipsychotics. They may also be used to treat bipolar disorder and depression. Examples include risperidone, olanzapine, and quetiapine.
3. Antiemetics: These drugs are used to treat nausea and vomiting. Examples include metoclopramide and prochlorperazine.
4. Dopamine agonists: While not technically dopamine antagonists, these drugs work by stimulating dopamine receptors and can be used to treat conditions such as Parkinson's disease. However, they can also have the opposite effect and block dopamine receptors in high doses, making them functionally similar to dopamine antagonists.

Common side effects of dopamine antagonists include sedation, weight gain, and movement disorders such as tardive dyskinesia. It's important to use these drugs under the close supervision of a healthcare provider to monitor for side effects and adjust the dosage as needed.

Purinergic P2Y receptor antagonists are a class of pharmaceutical compounds that block the activity of P2Y purinergic receptors, which are a type of G protein-coupled receptor found on the surface of various cells throughout the body. These receptors are activated by extracellular nucleotides such as ATP and ADP, and play important roles in regulating a variety of physiological processes, including inflammation, platelet aggregation, and neurotransmission.

P2Y receptor antagonists are used in the treatment of several medical conditions. For example, they can be used to prevent platelet aggregation and thrombosis in patients with cardiovascular disease or those at risk for stroke. They may also have potential therapeutic applications in the treatment of chronic pain, inflammatory disorders, and neurological conditions such as epilepsy and Parkinson's disease.

Some examples of P2Y receptor antagonists include clopidogrel (Plavix), ticlopidine (Ticlid), and cangrelor (Kengreal), which are used to prevent platelet aggregation and thrombosis, and suramin, a non-selective P2 receptor antagonist that has been investigated for its potential anti-cancer effects.

Neurokinin-1 (NK-1) receptor antagonists are a class of drugs that block the action of substance P, a neuropeptide involved in pain transmission and inflammation. These drugs work by binding to NK-1 receptors found on nerve cells, preventing substance P from activating them and transmitting pain signals. NK-1 receptor antagonists have been studied for their potential use in treating various conditions associated with pain and inflammation, such as migraine headaches, depression, and irritable bowel syndrome. Some examples of NK-1 receptor antagonists include aprepitant, fosaprepitant, and rolapitant.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

Muscarinic antagonists, also known as muscarinic receptor antagonists or parasympatholytics, are a class of drugs that block the action of acetylcholine at muscarinic receptors. Acetylcholine is a neurotransmitter that plays an important role in the parasympathetic nervous system, which helps to regulate various bodily functions such as heart rate, digestion, and respiration.

Muscarinic antagonists work by binding to muscarinic receptors, which are found in various organs throughout the body, including the eyes, lungs, heart, and gastrointestinal tract. By blocking the action of acetylcholine at these receptors, muscarinic antagonists can produce a range of effects depending on the specific receptor subtype that is affected.

For example, muscarinic antagonists may be used to treat conditions such as chronic obstructive pulmonary disease (COPD) and asthma by relaxing the smooth muscle in the airways and reducing bronchoconstriction. They may also be used to treat conditions such as urinary incontinence or overactive bladder by reducing bladder contractions.

Some common muscarinic antagonists include atropine, scopolamine, ipratropium, and tiotropium. It's important to note that these drugs can have significant side effects, including dry mouth, blurred vision, constipation, and confusion, especially when used in high doses or for prolonged periods of time.

Narcotic antagonists are a class of medications that block the effects of opioids, a type of narcotic pain reliever, by binding to opioid receptors in the brain and blocking the activation of these receptors by opioids. This results in the prevention or reversal of opioid-induced effects such as respiratory depression, sedation, and euphoria. Narcotic antagonists are used for a variety of medical purposes, including the treatment of opioid overdose, the management of opioid dependence, and the prevention of opioid-induced side effects in certain clinical situations. Examples of narcotic antagonists include naloxone, naltrexone, and methylnaltrexone.

Histamine H2 antagonists, also known as H2 blockers, are a class of medications that work by blocking the action of histamine on the H2 receptors in the stomach. Histamine is a chemical that is released by the body during an allergic reaction and can also be released by certain cells in the stomach in response to food or other stimuli. When histamine binds to the H2 receptors in the stomach, it triggers the release of acid. By blocking the action of histamine on these receptors, H2 antagonists reduce the amount of acid produced by the stomach, which can help to relieve symptoms such as heartburn, indigestion, and stomach ulcers. Examples of H2 antagonists include ranitidine (Zantac), famotidine (Pepcid), and cimetidine (Tagamet).

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CysLT1 leukotriene receptor antagonists inhibit the effects of nucleotides acting at P2Y receptors. Mamedova, L., Capra, V., ... Purinergic-induced signaling in C11-MDCK cells inhibits the secretory Na-K-Cl cotransporter. Brindikova, T.A., Bourcier, N., ... Purinergic receptors are part of a functional signaling system for proliferation and differentiation of human epidermal ... Identification of competitive antagonists of the P2Y1 receptor. Boyer, J.L., Romero-Avila, T., Schachter, J.B., Harden, T.K. ...
Title: P2Y11 receptor antagonist NF340 ameliorates inflammation in human fibroblast-like synoviocytes: An implication in ... P2RY11 purinergic receptor P2Y11 [Homo sapiens] P2RY11 purinergic receptor P2Y11 [Homo sapiens]. Gene ID:5032 ... purinergic receptor P2Y11provided by HGNC. Primary source. HGNC:HGNC:8540 See related. Ensembl:ENSG00000244165 MIM:602697; ... P2RY11 purinergic receptor P2Y11 [ Homo sapiens (human) ] Gene ID: 5032, updated on 23-Nov-2023 ...
Peptide-induced keratinocyte migration was mediated by purinergic receptors and metalloproteases. In contrast, SALPs did not ... or the non-selective P2 purinergic antagonist Pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid tetrasodium salt (PPADS; 50 ... Studies with melittin and SPINK9 point out that purinergic receptors are involved in the activation of metalloproteases30,31. ... Peptide-induced keratinocyte migration depends on purinergic receptors and metalloproteases.. (A) HaCaT cells were scratched ...
... which stimulates purinergic receptors on microglia in the dorsal horn. We identify serum- and glucocorticoid-inducible kinase-1 ... PSL mice was attenuated by antagonists of purinergic receptors. In this experiment, all antagonists were intrathecally injected ... 12), an antagonist of P2X1-4 receptors, nor MRS2578 (ref. 28), an antagonist of P2Y6 receptor, suppressed CORT-evoked ... Effects of antagonist P2X1-4 receptors TNP-ATP (3 nmol per mouse, i.th.) or antagonist P2Y6 receptor MRS2578 (30 nmol per mouse ...
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ATP is released during cell damage and acts on afferent sensory nerves through P2X3 purinergic receptors. The first antagonist ... Angiotensin II antagonists do not affect the cough reflex.. Drugs such as bisphosphonates or calcium channel antagonists may ... P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. ... While effective in animal models, these agents have failed in the clinic [130, 131]. The substance P antagonist orvepitant has ...
Purinergic P2Y Receptor Antagonists. *Prasugrel Hydrochloride. *Platelet Aggregation Inhibitors. *Piperazines. *Middle Aged ... INTRODUCTION: Prasugrel is a thienopyridyl P2Y12 antagonist with potent antiplatelet effects. At present, little is known about ...
Keywords: A 438079 hydrochloride, A 438079 hydrochloride supplier, Competitve, P2X7, antagonists, Receptors, Purinergic, ... Home / Pharmacology / Ion Channels / Ligand-gated Ion Channels / Purinergic (P2X) Receptors / Purinergic (P2X) Receptor ... A 438079 hydrochloride is a competitive P2X7 receptor antagonist (pIC50 = 6.9 for the inhibition of Ca2+ influx in the human ... Kowal et al (2015) Bile acid effects are mediated by ATP release and purinergic signalling in exocrine pancreatic cells. Mol ...
A covalent antagonist for the human adenosine A2A receptor. X Yang, G Dong, TJM Michiels, EB Lenselink, L Heitman, J Louvel ... Purinergic Signalling 13, 191-201, 2017. 30. 2017. Scanning mutagenesis in a yeast system delineates the role of the NPxxY (x) ... Discovery and mapping of an intracellular antagonist binding site at the chemokine receptor CCR2. AJM Zweemer, J Bunnik, M ... 4-dione Derivatives as Human Adenosine A3 Receptor Antagonists. L Xia, WAC Burger, JPD van Veldhoven, BJ Kuiper, TT van Duijl ...
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The appropriate selective agonists/antagonists for purinergic receptors as well as the respective enzyme inhibitors may ... The function of microglia is regulated by a whole array of purinergic receptors classified as P2Y12, P2Y6, P2Y4, P2X4, P2X7, ... The appropriate selective agonists/antagonists for purinergic receptors as well as the respective enzyme inhibitors may ... Regulation of Microglial Functions by Purinergic Mechanisms in the Healthy and Diseased CNS. Peter Illes ...
Effect of purinergic agonists and antagonists on insulin secretion from INS-1 cells (insulinoma cell line) and rat pancreatic ... The effects of purinergic agonists on insulin release are controversial in the literature. In our studies (mainly using INS-1 ... PPADS (100 mM), a P2X and P2Y1,4,6 receptor antagonist, was ineffective using either low or high concentrations of ATP and ... DPCPX (100 mM), an adenosine (A1) receptor antagonist, inhibited the inhibitory effects of both adenosine and of high ...
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Utilizing a variety of different P2X7 receptor antagonists, Agrawal et al. (2010) confirmed that but one substance decreased ... Purinergic signaling in bone tissue was initially proposed in the first. * Post author By cancerhugs ... Purinergic signaling in bone tissue was initially proposed in the first 1990s using the observation that extracellular ATP ... Another latest advancement in purinergic signaling using mouse versions has arisen because of J?rgensen and co-workers at the ...

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