Aminopyridines: Pyridines substituted in any position with an amino group. May be hydrogenated, but must retain at least one double bond.Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the TIBIAL NERVE and the PERONEAL NERVE.Diynes: Compounds with two triple bonds. Some of them are CYTOTOXINS.Central Nervous System Agents: A class of drugs producing both physiological and psychological effects through a variety of mechanisms. They can be divided into "specific" agents, e.g., affecting an identifiable molecular mechanism unique to target cells bearing receptors for that agent, and "nonspecific" agents, those producing effects on different target cells and acting by diverse molecular mechanisms. Those with nonspecific mechanisms are generally further classed according to whether they produce behavioral depression or stimulation. Those with specific mechanisms are classed by locus of action or specific therapeutic use. (From Gilman AG, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p252)4-Aminopyridine: One of the POTASSIUM CHANNEL BLOCKERS, with secondary effect on calcium currents, which is used mainly as a research tool and to characterize channel subtypes.Neural Conduction: The propagation of the NERVE IMPULSE along the nerve away from the site of an excitation stimulus.Butyrophenones: Compounds containing phenyl-1-butanone.Dothiepin: A tricyclic antidepressant with some tranquilizing action.Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.BooksAtaxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or PERIPHERAL NERVE DISEASES. Motor ataxia may be associated with CEREBELLAR DISEASES; CEREBRAL CORTEX diseases; THALAMIC DISEASES; BASAL GANGLIA DISEASES; injury to the RED NUCLEUS; and other conditions.Kv1.1 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.Cerebellar Ataxia: Incoordination of voluntary movements that occur as a manifestation of CEREBELLAR DISEASES. Characteristic features include a tendency for limb movements to overshoot or undershoot a target (dysmetria), a tremor that occurs during attempted movements (intention TREMOR), impaired force and rhythm of diadochokinesis (rapidly alternating movements), and GAIT ATAXIA. (From Adams et al., Principles of Neurology, 6th ed, p90)Acetazolamide: One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337)Isaacs Syndrome: A rare neuromuscular disorder with onset usually in late childhood or early adulthood, characterized by intermittent or continuous widespread involuntary muscle contractions; FASCICULATION; hyporeflexia; MUSCLE CRAMP; MUSCLE WEAKNESS; HYPERHIDROSIS; TACHYCARDIA; and MYOKYMIA. Involvement of pharyngeal or laryngeal muscles may interfere with speech and breathing. The continuous motor activity persists during sleep and general anesthesia (distinguishing this condition from STIFF-PERSON SYNDROME). Familial and acquired (primarily autoimmune) forms have been reported. (From Ann NY Acad Sci 1998 May 13;841:482-496; Adams et al., Principles of Neurology, 6th ed, p1491)Spinocerebellar Ataxias: A group of dominantly inherited, predominately late-onset, cerebellar ataxias which have been divided into multiple subtypes based on clinical features and genetic mapping. Progressive ataxia is a central feature of these conditions, and in certain subtypes POLYNEUROPATHY; DYSARTHRIA; visual loss; and other disorders may develop. (From Joynt, Clinical Neurology, 1997, Ch65, pp 12-17; J Neuropathol Exp Neurol 1998 Jun;57(6):531-43)Nystagmus, Pathologic: Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. (Adams et al., Principles of Neurology, 6th ed, p272)Vertigo: An illusion of movement, either of the external world revolving around the individual or of the individual revolving in space. Vertigo may be associated with disorders of the inner ear (EAR, INNER); VESTIBULAR NERVE; BRAINSTEM; or CEREBRAL CORTEX. Lesions in the TEMPORAL LOBE and PARIETAL LOBE may be associated with FOCAL SEIZURES that may feature vertigo as an ictal manifestation. (From Adams et al., Principles of Neurology, 6th ed, pp300-1)Spinocerebellar Degenerations: A heterogenous group of degenerative syndromes marked by progressive cerebellar dysfunction either in isolation or combined with other neurologic manifestations. Sporadic and inherited subtypes occur. Inheritance patterns include autosomal dominant, autosomal recessive, and X-linked.ThiosemicarbazonesMethemoglobinemia: The presence of methemoglobin in the blood, resulting in cyanosis. A small amount of methemoglobin is present in the blood normally, but injury or toxic agents convert a larger proportion of hemoglobin into methemoglobin, which does not function reversibly as an oxygen carrier. Methemoglobinemia may be due to a defect in the enzyme NADH methemoglobin reductase (an autosomal recessive trait) or to an abnormality in hemoglobin M (an autosomal dominant trait). (Dorland, 27th ed)ArchivesBiological Science Disciplines: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Directories as Topic: Lists of persons or organizations, systematically arranged, usually in alphabetic or classed order, giving address, affiliations, etc., for individuals, and giving address, officers, functions, and similar data for organizations. (ALA Glossary of Library and Information Science, 1983)Ribonucleotide ReductasesPyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Cytochrome-B(5) Reductase: A FLAVOPROTEIN oxidoreductase that occurs both as a soluble enzyme and a membrane-bound enzyme due to ALTERNATIVE SPLICING of a single mRNA. The soluble form is present mainly in ERYTHROCYTES and is involved in the reduction of METHEMOGLOBIN. The membrane-bound form of the enzyme is found primarily in the ENDOPLASMIC RETICULUM and outer mitochondrial membrane, where it participates in the desaturation of FATTY ACIDS; CHOLESTEROL biosynthesis and drug metabolism. A deficiency in the enzyme can result in METHEMOGLOBINEMIA.Location Directories and Signs: Directory signs or listings of designated areas within or without a facility.Crows: Common name for the largest birds in the order PASSERIFORMES, family Corvidae. These omnivorous black birds comprise most of the species in the genus Corvus, along with ravens and jackdaws (which are often also referred to as crows).Starlings: The family Sturnidae, in the order PASSERIFORMES. The starling family also includes mynahs and oxpeckers.Resins, Plant: Flammable, amorphous, vegetable products of secretion or disintegration, usually formed in special cavities of plants. They are generally insoluble in water and soluble in alcohol, carbon tetrachloride, ether, or volatile oils. They are fusible and have a conchoidal fracture. They are the oxidation or polymerization products of the terpenes, and are mixtures of aromatic acids and esters. Most are soft and sticky, but harden after exposure to cold. (From Grant & Hackh's Chemical Dictionary, 5th ed & Dorland, 28th ed)Birds: Warm-blooded VERTEBRATES possessing FEATHERS and belonging to the class Aves.Sorghum: A plant genus of the family POACEAE. The grain is used for FOOD and for ANIMAL FEED. This should not be confused with KAFFIR LIME or with KEFIR milk product.Insect Repellents: Substances causing insects to turn away from them or reject them as food.Powders: Substances made up of an aggregation of small particles, as that obtained by grinding or trituration of a solid drug. In pharmacy it is a form in which substances are administered. (From Dorland, 28th ed)Zea mays: A plant species of the family POACEAE. It is a tall grass grown for its EDIBLE GRAIN, corn, used as food and animal FODDER.Potassium Channel Blockers: A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.Tetraethylammonium: A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)Tetraethylammonium CompoundsHealth Care Surveys: Statistical measures of utilization and other aspects of the provision of health care services including hospitalization and ambulatory care.Health Surveys: A systematic collection of factual data pertaining to health and disease in a human population within a given geographic area.Potassium Channels: Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.Commerce: The interchange of goods or commodities, especially on a large scale, between different countries or between populations within the same country. It includes trade (the buying, selling, or exchanging of commodities, whether wholesale or retail) and business (the purchase and sale of goods to make a profit). (From Random House Unabridged Dictionary, 2d ed, p411, p2005 & p283)Economic Competition: The effort of two or more parties to secure the business of a third party by offering, usually under fair or equitable rules of business practice, the most favorable terms.

Three distinct anti-allergic drugs, amlexanox, cromolyn and tranilast, bind to S100A12 and S100A13 of the S100 protein family. (1/650)

To investigate the roles of calcium-binding proteins in degranulation, we used three anti-allergic drugs, amlexanox, cromolyn and tranilast, which inhibit IgE-mediated degranulation of mast cells, as molecular probes in affinity chromatography. All of these drugs, which have different structures but similar function, scarcely bound to calmodulin in bovine lung extract, but bound to the same kinds of calcium-binding proteins, such as the 10-kDa proteins isolated in this study, calcyphosine and annexins I-V. The 10-kDa proteins obtained on three drug-coupled resins and on phenyl-Sepharose were analysed by reversed-phase HPLC. It was found that two characteristic 10-kDa proteins, one polar and one less polar, were bound with all three drugs, although S100A2 (S100L), of the S100 family, was bound with phenyl-Sepharose. The cDNA and deduced amino acid sequence proved our major polar protein to be identical with the calcium-binding protein in bovine amniotic fluid (CAAF1, S100A12). The cDNA and deduced amino acid sequence of the less-polar protein shared 95% homology with human and mouse S100A13. In addition, it was demonstrated that the native S100A12 and recombinant S100A12 and S100A13 bind to immobilized amlexanox. On the basis of these findings, we speculate that the three anti-allergic drugs might inhibit degranulation by binding with S100A12 and S100A13.  (+info)

Differential discrimination of G-protein coupling of serotonin(1A) receptors from bovine hippocampus by an agonist and an antagonist. (2/650)

We have studied the effect of guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S), a non-hydrolyzable analogue of GTP, on agonist and antagonist binding to bovine hippocampal 5-hydroxytryptamine (5-HT)(1A) receptor in native membranes. Our results show that the specific binding of the agonist is inhibited with increasing concentrations of GTP-gamma-S along with a reduction in binding affinity. In sharp contrast to this, antagonist binding to 5-HT(1A) receptor shows no significant reduction and remains invariant over a large range of GTP-gamma-S concentrations. The binding affinity of the antagonist also remains unaltered. This shows that the agonist and the antagonist differentially discriminate G-protein coupling of 5-HT(1A) receptors from bovine hippocampus.  (+info)

Receptor density as a factor governing the efficacy of the dopamine D4 receptor ligands, L-745,870 and U-101958 at human recombinant D4.4 receptors expressed in CHO cells. (3/650)

1. The relationships between the density of dopamine D4.4 receptors and the agonist efficacies of L-745,870 (3-(4-[4-chlorophhenyl]piperazin-1-yl)-methyl-1H-pyrrolo [2, 3-b]pyridine) and U-101958 ((1-benzyl-piperidin-4-yl)-(3-isopropoxy-pyridin-2-yl)-methyl-a min e) were investigated in Chinese hamster ovary (CHO) cells, after treatment with the gene expression enhancer, sodium butyrate. 2. In CHO cells expressing D4.4 receptors (CHO/D4 cells), dopamine inhibited forskolin-stimulated cyclic AMP accumulation (Emax 56+/-1% inhibition, pEC50 7.4+/-0.1, n=10). U-101958 behaved as a partial agonist (39+/-7% the efficacy of dopamine, pEC50 8.1+/-0.3, n=4), whereas L-745,870 had no detectable agonist effect. 3. Receptor density, as estimated by [3H]-spiperone saturation binding was 240+/-30 fmol mg-1 protein (n=8) in CHO/D4 cell homogenates. It reached 560+/-150 (n=6), 1000+/-190 (n=4) and 840+/-120 (n=4) fmol mg-1 protein after treatment with sodium butyrate (5 mM) for 6, 18 and 48 h, respectively. 4. The increase in receptor density was associated with a gradual enhancement of the agonist effects (increased Emax and pEC50 values) of dopamine. The efficacy of U-101958 (relative to dopamine) doubled and L-745,870 was turned into a partial agonist (efficacy 49% relative to dopamine, pEC50 8. 6+/-0.2, n=6, after 48 h treatment with sodium butyrate). These agonist effects of U-101958 and L-745,870 could be antagonized by spiperone (0.1 microM) but not by raclopride (10 microM). 5. The results show that U-101958 and L-745,870 are partial agonists at human dopamine D4.4 receptors expressed in CHO cells. Their efficacy is governed by receptor density. Agonist effects of these two compounds in vivo cannot be excluded under circumstances of increased receptor levels.  (+info)

Design and characterization of orally active Arg-Gly-Asp peptidomimetic vitronectin receptor antagonist SB 265123 for prevention of bone loss in osteoporosis. (4/650)

The Arg-Gly-Asp (RGD)-binding integrin alpha(V)beta(3) is highly expressed on osteoclasts and has been proposed to mediate cell-matrix adhesion required for osteoclast-mediated bone resorption. Antagonism of this receptor should prevent stable osteoclast adhesion and thereby inhibit bone resorption. We have generated an orally bioavailable, nonpeptide RGD mimetic alpha(v)beta(3) antagonist, SB 265123, which prevents bone loss in vivo when dosed by oral administration. SB 265123 binds alpha(v)beta(3) and the closely related integrin alpha(v)beta(5) with high affinity (K(i) = 3.5 and 1.3 nM, respectively), but binds only weakly to the related RGD-binding integrins alpha(IIb)beta(3) (K(i) >1 microM) and alpha(5)beta(1) (K(i) >1 microM). The compound inhibits alpha(v)beta(3)-mediated cell adhesion with an IC(50) = 60 nM and more importantly, inhibits human osteoclast-mediated bone resorption in vitro with an IC(50) = 48 nM. In vivo, SB 265123 completely blocks bone resorption in a thyroparathyroidectomized rat model of acute bone resorption when dosed at 2.5 mg/kg/h by continuous i.v. infusion. When dosed orally with 3 to 30 mg/kg b.i.d. , in the ovariectomy-induced rat model of osteoporosis, SB 265123 prevents bone resorption in a dose-dependent fashion. This is the first report of an orally active alpha(v)beta(3) antagonist that is effective at inhibiting bone resorption when dosed in a pharmaceutically acceptable fashion. Such a molecule may provide a novel therapeutic agent for the treatment of postmenopausal osteoporosis.  (+info)

Preclinical pharmacokinetics and interspecies scaling of a novel vitronectin receptor antagonist. (5/650)

Allometric scaling may be used in drug development to predict the pharmacokinetics of xenobiotics in humans from animal data. Although allometry may be successful for compounds that are excreted unchanged or that are oxidatively metabolized (with corrections for metabolic capacity), it has been more challenging for compounds excreted primarily as conjugates in bile. (S)-10, 11-Dihydro-3-[3-(pyridin-2-ylamino)-1-propyloxy]-5H-dibenzo[ a, d]cycloheptene-10-acetic acid (SB-265123) is a novel alphavbeta3 ("vitronectin receptor") antagonist. In this study, the in vivo pharmacokinetics and in vitro plasma protein binding of SB-265123 were examined in four species: mice, rats, dogs, and monkeys. In monkeys and dogs, SB-265123 exhibited moderate clearance, whereas low clearance (<20% hepatic blood flow) was observed in the rat, and high clearance (>70% hepatic blood flow) was seen in the mouse. The concentration-time profiles indicated the possibility of enterohepatic recirculation; subsequent studies in bile duct-cannulated rats demonstrated extensive biliary excretion of an acyl-glucuronide of SB-265123. In allometric scaling to predict the disposition of SB-265123 in humans, various standard correction factors were applied, including protein binding, maximum lifespan potential, and brain weight; each failed to produce adequate interspecies scaling of clearance (r(2) < 0.72). Consequently, a novel correction factor incorporating bile flow and microsomal UDP-glucuronosyltransferase activity in each species was applied, demonstrating substantial improvement in the correlation of the allometric plot (r(2) = 0.96). This study demonstrates a novel allometric correction that may be applicable to compounds that undergo conjugation and biliary excretion.  (+info)

Specific inhibition of the eubacterial DNA ligase by arylamino compounds. (6/650)

All known DNA ligases catalyze the formation of a phosphodiester linkage between adjacent termini in double-stranded DNA via very similar mechanisms. The ligase family can, however, be divided into two classes: eubacterial ligases, which require NAD(+) as a cofactor, and other ligases, from viruses, archaea, and eukaryotes, which use ATP. Drugs that discriminate between DNA ligases from different sources may have antieubacterial activity. We now report that a group of arylamino compounds, including some commonly used antimalarial and anti-inflammatory drugs and a novel series of bisquinoline compounds, are specific inhibitors of eubacterial DNA ligases. Members of this group of inhibitors have different heterocyclic ring systems with a common amino side chain in which the two nitrogens are separated by four carbon atoms. The potency, but not the specificity of action, is influenced by the DNA-binding characteristics of the inhibitor, and the inhibition is noncompetitive with respect to NAD(+). The arylamino compounds appear to target eubacterial DNA ligase in vivo, since a Salmonella Lig(-) strain that has been rescued with the ATP-dependent T4 DNA ligase is less sensitive than the parental Salmonella strain.  (+info)

Reduction of 5-hydroxytryptamine (5-HT)(1A)-mediated temperature and neuroendocrine responses and 5-HT(1A) binding sites in 5-HT transporter knockout mice. (7/650)

The aim of the present study was to determine whether alterations in 5-hydroxytryptamine (5-HT)(1A) receptors would be found in knockout mice lacking the serotonin transporter (5-HTT). Hypothermic and neuroendocrine responses to the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) were used to examine the function of 5-HT(1A) receptors. Initial studies evaluated the dose-response and time course of 8-OH-DPAT-induced hypothermia and hormone secretion in normal CD-1 mice (the background strain of the 5-HTT knockout mice). 8-OH-DPAT dose-dependently produced hypothermic responses that peaked at 20 min postinjection. 8-OH-DPAT-induced hypothermia was blocked by the 5-HT(1A) antagonist WAY-100635. 8-OH-DPAT dose-dependently increased the concentrations of plasma oxytocin, corticotropin, and corticosterone. In the 5-HTT knockout (-/-) mice, the hypothermic response to 8-OH-DPAT (0.1 mg/kg s.c.) was completely abolished. Furthermore, 5-HTT-/- mice had significantly attenuated plasma oxytocin and corticosterone responses to 8-OH-DPAT. No significant changes in the hypothermic or hormonal responses to 8-OH-DPAT were observed in heterozygous (5-HTT+/-) mice. [(3)H]8-OH-DPAT- and [(125)I]MPPI [4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-iodobenzamido]ethyl] pip erazine]-binding sites in the hypothalamus and [(125)I]MPPI-binding sites in the dorsal raphe were significantly decreased in 5-HTT-/- mice. The results indicate that lack of the 5-HTT is associated with a functional desensitization of 5-HT(1A) receptor responses to 8-OH-DPAT, which may be a consequence, at least in part, of the decrease in density of 5-HT(1A) receptors in the hypothalamus and dorsal raphe of 5-HTT-/- mice.  (+info)

Evidence that somatostatin sst2 receptors mediate striatal dopamine release. (8/650)

1 Somatostatin (SRIF) is a cyclic tetradecapeptide present in medium-sized aspiny interneurones in the rat striatum. We have previously shown that exogenous SRIF potently stimulates striatal dopamine (DA) release via a glutamate-dependent mechanism. We now report the ability of the selective sst2 receptor agonist, BIM-23027, to mimic this effect of SRIF. 2 In vivo microdialysis studies were performed in anaesthetized male Wistar rats. In most experiments, compounds were administered by retrodialysis into the striatum for 15 min periods, 90 min and 225 min after sampling commenced, with levels of neurotransmitters being measured by HPLC with electrochemical and fluorescence detection. 3 BIM-23027 (50 and 100 nM) stimulated DA release with extracellular levels increasing by up to 18 fold. 4 Prior retrodialysis of BIM-23027 (50 nM) abolished the effects of subsequent administration of SRIF (100 nM). 5 The agonist effects of both BIM-23027 and SRIF were abolished by the selective sst2 receptor antagonist, L-Tyr8-CYN-154806 (100 nM). 6 The AMPA/kainate receptor antagonist, DNQX (100 microM), abolished the agonist effects of BIM-23027 as previously shown for SRIF. 7 This study provides evidence that the sst2 receptor mediates the potent dopamine-releasing actions observed with SRIF in the rat striatum. Dopamine release evoked by both peptides appears to be mediated indirectly via a glutamatergic pathway. Other subtype-specific somatostatin receptor ligands were unable to elicit any effects and therefore we conclude that no other somatostatin receptor types are involved in mediating the dopamine-releasing actions of SRIF in the striatum.  (+info)

*3-Aminopyridine

... is an aminopyridine. It can be used in the synthesis of organic ligand 3-pyridylnicotinamide 3-Aminopyridine ... Allen, C. F. H.; Wolf, Calvin N. (1950). "3-Aminopyridine". Organic Syntheses. 30: 3. doi:10.15227/orgsyn.030.0003. ; ... 3-Aminopyridine can easily be absorbed through the skin. It is fatal if swallowed or absorbed through the skin. High ...

*2-Aminopyridine

... is an organic compound with the formula H2NC5H4N. It is one of three isomeric aminopyridines. It is a ... CS1 maint: Uses authors parameter (link) MSDS CDC - NIOSH Pocket Guide to Chemical Hazards - 2-Aminopyridine. ... "2-Aminopyridine". Immediately Dangerous to Life and Health Concentrations (IDLH). National Institute for Occupational Safety ... is less important for 2-aminopyridine. "NIOSH Pocket Guide to Chemical Hazards #0026". National Institute for Occupational ...

*4-Aminopyridine

... is also used under the trade name Avitrol as 0.5% or 1% in bird control bait. It causes convulsions and, ... 4-Aminopyridine is a potent convulsant and is used to generate seizures in animal models for the evaluation of antiseizure ... 4-Aminopyridine (4-AP, fampridine, dalfampridine) is an organic compound with the chemical formula C5H4N-NH2. The molecule is ... The use of 4-aminopyridine in bird control has been criticized by the Humane Society of the United States. Fampridine has been ...

*3-Aminopyridine-2-carboxaldehyde thiosemicarbazone

... (3-AP, also called Triapine) is a substance that is being studied in the ...

*Nicotinamide

Collective Volume, 4, p. 706 Allen, C. F. H.; Wolf, Calvin N. (1950). "3-Aminopyridine". Organic Syntheses. 30: 3. doi:10.15227 ... and from 3-aminopyridine by reaction with a solution of sodium hypobromite, prepared in situ from bromine and sodium hydroxide ...

*Sodium hypobromite

Allen, C. F. H.; Wolf, Calvin N. (1950). "3-Aminopyridine". Organic Syntheses. 30: 3. doi:10.15227/orgsyn.030.0003. ; ... such as in the synthesis of 3-aminopyridine from nicotinamide. Schmeisser, M. (1963). "Sodium Hypobromite". In Brauer, Georg. ...

*[email protected]

6b 2-aminopyridine; 6 2-pyridoxine/2-aminopyridine; 7a Adenine; 7b Thymine; 7 Adenine/thymine WC; 8a Methane; 8 Methane dimer; ...

*Amifampridine

4-Aminopyridine "Firdapse Summary of Product Characteristics" (PDF). EMA. February 11, 2010. See EMA Index page, product tab ... Solari, A.; Uitdehaag, B.; Giuliani, G.; Pucci, E.; Taus, C. (2002). "Aminopyridines for symptomatic treatment in multiple ... Sedehizadeh, S; Keogh, M; Maddison, P (2012). "The use of aminopyridines in neurological disorders". Clinical neuropharmacology ... more specifically 4-aminopyridine-3-ylammonium dihydrogen phosphate. This salt forms prismatic, monoclinic crystals (space ...

*Betty Harris (scientist)

Harris, Betsy Wright (1975). Reactions of 2-aminopyridine with picryl halides. University of New Mexico. Retrieved 23 March ... "Reactions of 2-aminopyridine with picryl halides". After gaining her PhD, Harris moved to do research at Los Alamos National ...

*Yellapragada Subbarow

Subbarow, Y.; Dann, W.J. (1938). "The inactivity of β-aminopyridine in blacktongue". Journal of the American Chemical Society. ... Subbarow, Y.; Dann, W.J.; Meilman, E. (1938). "The effect of β-aminopyridine in experimental blacktongue". Journal of the ...

*Centre for Human Reproductive Science

Gu Y, Kirkman-Brown JC, Korchev Y, Barratt CL, Publicover SJ (October 2004). "Multi-state, 4-aminopyridine-sensitive ion ...

*Pyridyne

The reaction of 4-bromopyridine with sodium in liquid ammonia gives both 3-aminopyridine and 4-aminopyridine through the 3,4- ... The methylthio and amino pyridines were found to be formed in the same ratio. In 1972 Kramer and Berry inferred the formation ...

*Pyridine

Here, sodium amide is used as the nucleophile yielding 2-aminopyridine. The hydride ion released in this reaction combines with ... The unsubstituted pyridine ring degrades more rapidly than picoline, lutidine, chloropyridine, or aminopyridines, and a number ...

*Xylazine

Combining yohimbine and 4-aminopyridine in an effort to antagonize xylazine is superior as compared to the administration of ... Ndeereh, DR; Mbithi, PM; Kihurani, DO (June 2001). "The reversal of xylazine hydrochloride by yohimbine and 4-aminopyridine in ... Effects of xylazine are also reversed by the analeptics 4-aminopyridine, doxapram, and caffeine, which are physiological ...

*N-(p-amylcinnamoyl)anthranilic acid

"4-Aminopyridine and the early outward current of sheep cardiac Purkinje fibers". J Gen Physiol 1979;73:139-157. Zygmunt AC, ... Li GR, Feng J, Wang Z, Fermini B, Nattel S. "Comparative mechanisms of 4-aminopyridine-resistant Ito in human and rabbit atrial ...

*2-Bromopyridine

It can be prepared from 2-aminopyridine via diazotization followed by bromination. It reacts with butyllithium to give 2- ...

*4-Pyridylnicotinamide

It is synthesized through the reaction of nicotinoyl chloride and 4-aminopyridine. Gardner, T. S.; Wenis, E.; Lee, J. (1954). " ...

*2-Pyridone

"Infrared studies of tautomerism in 2-hydroxypyridine 2-thiopyridine and 2-aminopyridine". Spectrochimica Acta Part A: Molecular ...

*Paroxysmal depolarizing shift

2010), MODULATION OF NICKEL-INDUCED BURSTING WITH 4-AMINOPYRIDINE IN LEECH RETZIUS NERVE CELLS. http://serbiosoc.org.rs/arch_ ...

*Ipidacrine

This compound is a derivative of 4-aminopyridine and is structurally similar to tacrine. Ipidacrine is a reversible ...

*Nicotinamide ribonucleoside uptake transporters

"PnuC and the utilization of the nicotinamide riboside analog 3-aminopyridine in Haemophilus influenzae". Antimicrobial Agents ...

*Mushi Santappa

"Hydrogen bonding and tautomeric equilibria in Schiff bases derived from 2-amino pyridines: electronic spectral evidence for ...

*Feral pigeon

In the United States market, only 4-aminopyridine (Avitrol) and DRC-1339 remain registered by EPA. DRC-1339 is limited to USDA ...

*Tetraethylammonium

"Ion dependence of the release of noradrenaline by tetraethylammonium and 4-aminopyridine from cat splenic slices." Br. J. ...

*Neurotoxin

"Significant Effects of 4-aminopyridine and Tetraethylammonium in the Treatment of 6-hydroxydopamine-induced Parkinson's Disease ...
4-Aminopyridines undergo surprisingly rapid and highly-selective H/D exchange at C-2 and C-6 in neutral D2O upon microwave irradiation at only 190 °C for 2 h in a sealed vessel. This method contrasts and complements acid-mediated H/D exchange, requires no catalyst and is appropriate for the synthesis of deuterium isotop-ologues of N- and C-substituted 4-aminopyridines and a ben-zofused (quinoline) analogue.. ...
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This paper describes a protocol for imidazo[1,2-a]pyridine-2-carboxylic acids synthesis directly from condensation of substituted 2-aminopyridines and bromopyruvic acid. The recipe is applicable to a wide range of aminopyridines and can be telescoped with an amide formation to obtain Imidazo[1,2-a]pyridine-2-carboxamides in one continuous process.. ...
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1QBV: Structural analysis of thrombin complexed with potent inhibitors incorporating a phenyl group as a peptide mimetic and aminopyridines as guanidine substitutes.
Flupirtine Maleate is a medicine available in a number of countries worldwide. A list of US medications equivalent to Flupirtine Maleate is available on the Drugs.com website.
In people whos cancers have a PIK3CA mutation, this trial will be evaluating the drug BKM120 as a possible treatment. BKM120 works by blocking the phosphatidylinositol-3-kinase (PI3K)pathway, thereby inhibiting tumor growth and survival.. The purpose of this study is to learn if the study drug BKM120 can shrink or slow the growth of your tumor. The safety of BKM120 will also be studied. Your physical state, symptoms, change in the size of your tumor, and laboratory findings obtained while you are on study will help the research team decide if BKM120 is safe and effective in patients with advanced cancers. ...
Abstract: The lymphoid neoplasms are a heterogeneous group of diseases caused by genetic alterations that were originated from hematopoietic progenitor cells of lymphoid origin, leading to uncontrolled clonal proliferation of B or T cells, and to the development of lymphoid leukemias and lymphomas. These findings emphasize the involvement of different signaling pathways involved in both the development and the maintenance of hematological malignancies. Constitutive activation of the PI3K /AKT/mTOR signaling pathway is well described for acute lymphoblastic leukemia T cells (T-ALL), recently been identified in animal models, that the activity of PI3K cooperates with the development of Burkitts lymphoma (LB).Thus, the role of the PI3K / AKT / mTOR pathway in cell growth and survival, two important features of leukemogenesis, morphed into a potential drug target. Following this perspective, the present study aimed to evaluate the therapeutic potential of NVP-BKM120, a pan-PI3K inhibitor class I in ...
Flupirtine is a pyridine derivative that is in clinical use as a nonopioid analgesic. It was approved for the treatment of pain in 1984 in Europe. It is not approved for use in the U.S. or Canada, but is currently in phase II trials for the treatment of fibromyalgia.
There is a need to improve treatments for metastatic breast cancer. Here we show activation of the phosphoinositide 3-kinase (PI3K) and MAP kinase (MAPK) pathways in a MMTV-CreBRCA1f/fp53+/- mouse model of breast cancer. When treated with the pan-Class IA PI3K-inhibitor NVP-BKM120, tumor doubling was delayed from 5 to 26 days. NVP-BKM120 reduced AKT phosphorylation, tumor cell proliferation and angiogenesis. Resistant tumors maintained suppression of AKT phosphorylation but exhibited activation of the MAPK-pathway at the "pushing margin". Surprisingly, PI3K-inhibition increased indicators of DNA damage, poly-ADP-ribosylation and γH2AX, but decreased Rad51 focus formation, suggesting a critical role of PI3K activity for Rad51 recruitment. PARP-inhibitor Olaparib alone attenuated tumor growth modestly; however, the combination of NVP-BKM120 and Olaparib delayed tumor doubling to more than 70 days in the mouse model and over 50 days in xenotransplants from human BRCA1-related tumors, suggesting ...
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In the reaction of 2,6-dichloropyridine and 2,6-dichloro-3-phenylpyridine with potassium amide in liquid ammonia at -70°C, formation of derivatives of 4,4-bipyridyl and 3,4-bipyridyl is observed. The 4,4 coupling products are far in excess to the 3,4 coupling products. When the reaction is carried out at -70°C in the presence of potassium permanganate, the corresponding 4-aminopyridines are the main products. 2-Chloro-6-phenoxypyridine is very unreactive with this aminating reagent at -70°C as well as -33°C, but in the presence of potassium permanganate at -33°C 4-amino-2-chloro-6-phenoxypyridine is formed in fair yield. The mechanisms of the formation of the bipyridyls and 4-aminopyridines are presented.. ...
Looking for online definition of 3,4-diaminopyridine in the Medical Dictionary? 3,4-diaminopyridine explanation free. What is 3,4-diaminopyridine? Meaning of 3,4-diaminopyridine medical term. What does 3,4-diaminopyridine mean?
Abstract : 2-Aminopyridine (2-AP) and 2,6-diaminopyridine (2,6-DAP) are two derivatives of aminopyridines that act as animportant organic intermediates, mostly used in medicines, dyes and organic sensors. The aim of the study was to evaluate theimpact of biofield energy treatment on isotopic abundance ratios of 2H/1H, 13C/12C, or 15N/14N, in aminopyridine derivativesusing gas chromatography-mass spectrometry (GC-MS). The 2-AP and 2,6-DAP samples were divided into two parts: controland treated. The control sample remained as untreated, while the treated sample was further divided into four groups as T1, T2,T3, and T4. The treated group was subjected to Mr. Trivedis biofield energy treatment. The GC-MS spectra of 2-AP and 2,6-DAP showed five and six m/z peaks respectively due to the molecular ion peak and fragmented peaks of aminopyridinederivatives. The isotopic abundance ratio of 2H/1H, 13C/12C, or 15N/14N were calculated for both the derivatives and significantalteration was found in the ...
Aminopyridines have recently become the focus of extensive studies, mainly because of their wide use as building blocks for synthetic transformations (Peng et al., 2001; Leung et al., 2002). Carboxylic acids are important in crystal engineering due to their strong and directional O-H···O and N-H···O hydrogen bonds; this is the main hydrogen-bonding motif often encountered in carboxylic acid-amine complexes (Banerjee & Murugavel, 2004; Lautie & Belabbes, 1996). Here, we report the synthesis and crystal structure of the title compound, (I).. The asymmetric unit of the title compound, (Fig 1), contains one 2,3-diaminopyridinium cation, one sorbate anion and one neutral sorbic acid molecule. The 2,3-diaminopyridinium cation is planar with a maximum deviation of 0.013 (2) Å for atom C2. Protonation of atom N1 has resulted in a slight increase in the angle C1-N1-C5 [123.71 (17)°]. The sorbate anion and sorbic acid moiety is in the EE configuration. The structure is significantly different ...
PRIMARY OBJECTIVES:. I. To determine the maximum tolerated dose (MTD) of BKM120 (PI3K inhibitor BKM120) in combination with fulvestrant.. II. To evaluate the toxicity profile of BKM120 in combination with fulvestrant.. SECONDARY OBJECTIVES:. I. To evaluate the toxicity profile of BKM120 in combination with fulvestrant when administered for at least 3 months.. II. To determine the steady state blood concentrations of BKM120 when combined with fulvestrant.. III. To evaluate the anti-tumor effect (partial response [PR], complete response [CR], stable disease [SD], and progressive disease [PD]) of BKM120 in combination with fulvestrant in patients with ER+ metastatic breast cancer.. TERTIARY OBJECTIVES:. I. To examine baseline tumor specimens for phosphatidylinositol 3-kinase (PI3K) pathway abnormalities, and to correlate with treatment response.. II. To examine the PIK3 catalytic alpha polypeptide (PIK3CA) mutation status in circulating deoxyribonucleic acid (DNA) at baseline and following study ...
Lawrence LeBlond for redOrbit.com - Your Universe Online. A drug that is normally prescribed for asthma patients is breathing new life as a potential treatment option for people who suffer from diabetes and obesity. The drug, amlexanox, was demonstrated to reverse obesity, diabetes and fatty liver in mice in a new study, published this week in the journal Nature Medicine.. The finding comes from the research lab of Alan Saltiel, the Mary Sue Coleman director of the Life Sciences Institute at the University of Michigan. Saltiel explained that amlexanox is currently prescribed to treat asthma in Japan and canker sores in the US, but the new research shows that it may also be a viable option for treatment of obesity and diabetes.. "One of the reasons that diets are so ineffective in producing weight loss for some people is that their bodies adjust to the reduced calories by also reducing their metabolism, so that they are defending their body weight," Saltiel said in a statement. "Amlexanox seems ...
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There is limited real-world evidence of the demographic and clinical characteristics, as well as resource utilizations and associated costs, among COPD patients who were on roflumilast vs other maintenance combination medications. Results from this study indicate that, at baseline, most patients in the roflumilast cohort use roflumilast along with other maintenance medications as combination therapy. The roflumilast cohort showed a larger proportion of patients with ,3 drug classes in their combination therapy, a greater comorbidity burden, more severe COPD conditions, and higher exacerbation history compared with the nonroflumilast cohort. These results are not unexpected. Roflumilast is a relatively new drug indicated for the treatment of severe COPD, and previous research has suggested that newer drugs are more likely to be prescribed to patients who have failed to respond to other treatments, tend to be sicker, or both (Schneeweiss 2011). In addition, the GOLD guidelines recommend adding ...
Roflumilast has been shown to reduce exacerbations in patients at risk of these episodes, but whether this occurs on top of the effect of other therapy has been less clear. In this pre-specified combined analysis of data from two large randomised clinical trials, roflumilast decreased the rate of COPD exacerbations and improved lung function (pre- and post-bronchodilator FEV1) despite concomitant treatment with LABAs. In addition, the time to onset of the first, second and third moderate or severe exacerbation was delayed by roflumilast regardless of concomitant LABA use, while the frequency of adverse events associated with roflumilast treatment was not different in those with or without LABAs. The relative reduction in moderate or severe exacerbation rates in patients treated with LABAs was 20.7% and the corresponding number needed to treat with roflumilast to prevent one moderate or severe exacerbation per year was low (3.2).. Although the treatment effect of roflumilast together with ...
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Learn about the potential side effects of roflumilast. Includes common and rare side effects information for consumers and healthcare professionals.
The goal of this clinical research study is to learn if BKM120 (buparlisib) can help to control glioblastoma and/or gliosarcoma. Researchers also want to learn more about how much study drug is in different areas of the body at different time points. The safety of this drug will also be studied. BKM120 is designed to block a protein that is important to the growth and division of cancer cells, which may cause the cells to die.
This pilot study will investigate the efficacy and tolerability of BKM 120 for the treatment of refractory or residual aggressive B-cell non-Hodgkin lymphoma.
The purpose of this study is to find out the good and bad effects that occur when BKM120 is added to standard chemotherapy with carboplatin and paclitax
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45. At least one chemical entity of claim 1 wherein the compound of Formula 1 is selected frommethyl 4-[(2-fluoro-3-{[(6-methyl(3-pyridyl))amino]carbonylamino}phenyl)methyl]p- iperazinecarboxylate;N-({3-fluoro-5-[(3-pyridylamino)carbonylamino]phenyl}- methyl)methoxy-N-methylcarboxamide;N-[(3-fluoro-5-{[(6-methyl(3-pyridyl))a- mino]carbonylamino}phenyl)methyl]methoxy-N-methylcarboxamide;N-[3-({[(dime- thylamino)sulfonyl]methylamino}methyl)-5-fluorophenyl](3-pyridylamino)carb- oxamide;N-[3-({[(dimethylamino)sulfonyl]methylamino}methyl)-5-fluorophenyl- ][(6-methyl(3-pyridyl))amino]carboxamide;N-(3-({[(ethylsulfonyl)methylamin- o]methyl)-5-fluorophenyl)[(6-methyl(3-pyridyl))amino]carboxamide;methyl 4-({3-fluoro-5-[(3-pyridylamino)carbonylamino]phenyl}methyl)piperazinecar- boxylate;N-(3-{[4-(ethylsulfonyl)piperazinyl]methyl}-5-fluorophenyl)(3-pyr- idylamino)carboxamide;methyl 4-[(3-fluoro-5-{[(6-methyl(3-pyridyl))amino]carbonylamino}phenyl)methyl]p- ...
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Roflumilast is a targeted, oral, once-daily administered phosphodiesterase 4 (PDE4) inhibitor with clinical efficacy in COPD. Results from in vitro studies with roflumilast indicate that roflumilast has anti-inflammatory properties that may be applicable for the treatment of COPD. In this cross-over study, 38 patients with COPD (mean (SD) age 63.1 (7.0) y, post-bronchodilator FEV1 61.0 (12.6) %predicted) received 500 μg roflumilast or placebo once daily for 4 weeks. Induced sputum samples were collected prior to and after 2 and 4 weeks of treatment. Differential and absolute cell counts were determined in whole sputum samples. Markers of inflammation were determined in sputum supernatants and blood. Spirometry was performed weekly. Roflumilast significantly reduced the absolute number of neutrophils and eosinophils per gram of sputum, compared with placebo, by 35.5% (95%CI 15.6, 50.7; p=0.0017) and 50.0% (26.8, 65.8; p=0.0005), respectively. The relative proportion of sputum neutrophils and ...
0055]The matrix in which the aminopyridine is homogeneously dispersed provides a sustained release of the aminopyridine into the plasma of the patient. Polymeric matrices suitable for controlling the release rate of aminopyridines for use in the pharmaceutical compositions of the present invention include hydrophilic polymers; hydrophobic polymers or mixtures of hydrophilic and/or hydrophobic polymers that are capable of forming sustained-release dosage formulation in combination with an aminopyridine. Such matrices are also capable of preventing degradation and loss of the aminopyridine from the composition. Examples of suitable matrices either alone or in combination include but are not limited to hydroxyalkylcelluloses, such as hydroxypropylcellulose and HPMC, hydroxyethyl cellulose, alkylcelluloses such as ethycellulose and methylcellulose, carboxymethylcellulose; sodium carboxymethylcellulose, hydrophilic cellulose derivatives, polyethylene oxide, polyethylene glycol, polyvinylpyrrolidone; ...
Professor Michael Strupp, MD, FRCP, FANA, FEAN is a Scientific Founder and Consultant for IntraBio Inc. Professor Strupp is a Professor at the University of Munich, Germany in the Department of Neurology and German Centre for Vertigo and Balance Disorders. His expertise is in therapy for vestibular, ocular motor, and cerebellar disorders. Professor Strupps research has demonstrated the effectiveness of vestibular exercises in acute vestibular neuritis in a controlled clinical trial, and introduced three new therapeutic principles: aminopyridines, as potassium channel blockers, for the treatment of downbeat, upbeat and central positioning nystagmus as well as episodic ataxia type 2; chlorzoxazone for the therapy of downbeat nystagmus; and, more recently, acetyl-DL-leucine for the treatment of ataxias and Niemann-Pick Type C. His study demonstrating the benefit of steroids in acute vestibular neuritis, a placebo-controlled, four-arm trial was published in the NEJM. Currently, Professor Strupp is ...
Roflumilast reduces inflammation in the lungs that leads to COPD (chronic obstructive pulmonary disease). Roflumilast is used to prevent worsening of symptoms in people with severe chronic obstructive pulmonary disease (COPD). Roflumilast is not a bronchodilator. It will not treat a bronchospasm attack that has already...
roflumilast: Find the most comprehensive real-world treatment information on roflumilast at PatientsLikeMe. 0 patients with fibromyalgia, multiple sclerosis, major depressive disorder, generalized anxiety disorder, diabetes type 2, post-traumatic stress disorder, systemic lupus erythematosus, bipolar disorder, Parkinsons disease, panic disorder, rheumatoid arthritis, high blood pressure (hypertension), myalgic encephalomyelitis/chronic fatigue syndrome, persistent depressive disorder (dysthymia), amyotrophic lateral sclerosis, epilepsy, migraine, hypothyroidism, osteoarthritis, traumatic brain injury, bipolar II disorder, attention deficit/hyperactivity disorder, asthma, social anxiety disorder, high cholesterol (hypercholesterolemia), irritable bowel syndrome, idiopathic pulmonary fibrosis, gastroesophageal reflux disease, bipolar I disorder or psoriasis currently take roflumilast.
Roflumilast (trade names Daxas, Daliresp) is a drug that acts as a selective, long-acting inhibitor of the enzyme phosphodiesterase-4 (PDE-4). It has anti-inflammatory effects and is used as an orally administered drug for the treatment of inflammatory conditions of the lungs such as chronic obstructive pulmonary disease (COPD).[5][6][7][8] In June 2010, it was approved in the EU for severe COPD associated with chronic bronchitis.[9] In March 2011, it gained FDA approval in the US for reducing COPD exacerbations.[10] ...
Amlexanox is an antiallergic drug, clinically effective for atopic diseases, especially allergic asthma and rhinitis. Amlexanox as a topical paste is a well tolerated treatment of recurrent aphthous ulcers. Recurrent aphthous ulcer (RAU) is the most prevalent oral mucosal disease in humans, estimated to affect between 5% and 50% of the general population.
Micromedex Consumer Medication Information. Published: March 1, 2016Roflumilast (By mouth)roe-FLUE-mi-lastPrevents exacerbations (flare-ups) of chronic obstructive pulmonary disease (COPD).
Purpose: Cetuximab, an antibody targeting the epidermal growth factor receptor (EGFR), is active in colorectal cancer (CRC). However, response rates range from only 10% to 20%. Here, we investigate hepatocyte growth factor (HGF)-dependent mesenchymal-epithelial transition factor (MET) activation as a mediator of cetuximab resistance through signal diversification in CRC cell lines. Experimental Design: DiFi, GEO, and LIM1215 cells were treated with varying concentrations and combinations of EGF, HGF, cetuximab, and PHA-665752 (a highly specific MET kinase inhibitor). Biological end points included proliferation, cell-cycle arrest, and apoptosis. Proliferation was measured using WST-1 assays and synergy investigated via isobolograms. Expression and signaling were examined using immunoblotting. Results: EGFR and MET are co-expressed in these CRC cell lines, and dual receptor activation synergistically increased proliferation. Cetuximab inhibited cell growth by 60% to 80%, with an associated ...
BACKGROUND: Tramadol is an opioid analgesic licensed for use in moderate to severe pain. It is considered as a low risk for abuse, so control regulations are not as stringent as for strong opioids such as morphine. It has a potential role as a step 2 option of the World Health Organization (WHO) analgesic ladder. OBJECTIVES: To assess the benefits and adverse effects of tramadol with or without paracetamol (acetaminophen) for cancer-related pain. SEARCH METHODS: We searched the following databases using a wide range of search terms: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS ...
Success demonstrate that neither W94A nor W127A sig nicantly hinder LRT selleck accumulation, whereas wild kind A3G and E259Q reduced these ranges by selleck chemical NVP-BKM120 forty 60% for each viruses.A3G and E259Q had significantly much more dramatic effects on integration with measured reductions of 94 and 89% for HIV and 92 and 81% for MoMLV, respectively.These effects clearly reveal the marginal part of de amination in preventing these two early measures within the infec tion. Then again, W94A had no signicant effect on decreasing the proviral integration of both MoMLV or HIV. Equally, W127A did not lessen the integration of HIV, but appeared to possess a slight impact on MoMLV. Inactivation of the deaminase activity from the W94A RNA binding mutant had no detectable impact on LRT accumulation or integration, which once more supports that deamination is not really a serious contributor in preventing these specic processes. Hypermutation will not have an impact on MoMLV particle release ...
When added to standard bronchodilator therapies in the two six-month studies, a clear trend for the reduction of exacerbations was observed with roflumilast, over and above what was achieved with these therapies alone. Advair Diskus Help To Pay Buy Cheap Torsemide - ...
The substance is irritating to the eyes and skin. The substance may cause effects on the central nervous system. This may result in convulsions and respiratory depression. Exposure could cause an increase in blood pressure. Exposure far above the OEL could cause death. Effects of long-term or repeated exposure ...
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Clinical Trials - clinicaltrials.gov Aim of the work Assessment of early outcome of using Roflumilast in patients with bronchiectasis regarding: - Severity of s...
PND-1186, also known as SR-2156 and VS-4718, is a potent FAK inhibitor with a 50% inhibitory concentration (IC50) of 1.5 nM in vitro. PND-1186 has an IC50 of ~100 nM in breast carcinoma cells. Notably, 1.0 µM PND-1186 (|5-fold above IC50) had limited effects on cell proliferation. However, under non-adherent conditions as spheroids and as colonies in soft agar, 0.1 µM PND-1186 blocked FAK and p130Cas tyrosine phosphorylation, promoted caspase-3 activation, and triggered cell apoptosis. PND-1186 inhibited 4T1 breast carcinoma subcutaneous tumor growth correlated with elevated tumor cell apoptosis and caspase 3 activation.
3 and examined their appearance through real-time PCR with hypoxia-induced GC cells (after a day in 1% O2 for the SGC-7901 AGS and BGC-823 gastric cancers cells) in accordance with normoxia induced GC cells. Recently identified "type":"entrez-nucleotide" attrs :"text":"AK123072″ term_id :"34528533″AK123072 often up-regulated in gc and induced by hypoxia in gc cells Among the differentially portrayed lncRNAs among hypoxia induced GC cells and normoxia-induced GC cells we had been particularly thinking about lncRNA-"type":"entrez-nucleotide" attrs :"text":"AK123072″ term_id :"34528533″AK123072 because its appearance increased around 6.20±1.65-fold upon hypoxia treatment in every 3 cell lines. Hence we examined the part of "type":"entrez-nucleotide" attrs :"text":"AK123072″ term_id :"34528533″AK123072 which is an intronic antisense BKM120 (NVP-BKM120) lncRNA. Given that "type":"entrez-nucleotide" attrs :"text":"AK123072″ term_id :"34528533″AK123072 is definitely induced by hypoxia ...
Over 30% of all incurable lung adenocarcinomas have a KRAS mutation and, despite the impressive advances in targeted therapies over past several years, no appro...
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The onion layers ended up incubated from 25��C AZD6738 pertaining to 18?h, then looked at by lazer checking microscopy (LSM700; Carl Zeiss).
Most prostate cancer-related deaths are due to advanced disease with patients with metastatic prostate cancer having a 5-year survival rate of only 34%. Overexpression of c-Met receptor tyrosine kinase has been highly associated with prostate cancer progression and metastasis. In the present studies, the effect of BMS-777607, a selective and potent small-molecule Met kinase inhibitor that has been advanced to clinical evaluation, on hepatocyte growth factor (HGF)-mediated cell functions and signaling pathways was evaluated in c-Met-expressing PC-3 and DU145 prostate cancer cells. BMS-777607 treatment had little effect on tumor cell growth but inhibited cell scattering activated by exogenous HGF, with almost complete inhibition at 0.5 μmol/L in PC-3 and DU145 cells. This agent also suppressed HGF-stimulated cell migration and invasion in a dose-dependent fashion (IC50 , 0.1 μmol/L) in both cell lines. Mechanistically, nanomolar doses of BMS-777607 potently blocked HGF-stimulated c-Met ...
A month earlier published Relyea paper in Ecological Applications reporting that gradual amounts of malathion - primary is too small to kill directly develop leopard tadpoles instead a biological chain reaction that it triggered deprived of her - the most popular insecticide in the United States food source pharmacie en ligne . As a result, nearly half the tadpoles in the experiment did not reach maturity and would have died in nature.. Roflumilast, a once-daily tablet , would be the first in a whole new class of treatment for COPD, if it receives the approval of the authorities in Europe and the U.S. . The phase III placebo-controlled trials of roflumilast evaluated the treatment in two 12-month and two six-month studies , in 500 patients ten countries. Details of the results of four studies published in The Lancet on 29 August to be published.. ...
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In an unbiased gene expression and chemical genomics screen, PDE4B was found as one of the highest expressed genes in glucocorticoid-resistant acute lymphoid leukemia (ALL).37 Furthermore, PDE4B variants were associated with a higher rate of relapse in childhood ALL.38 Corroborating these observations, genes associated with glucocorticoid resistance in ALL were enriched in DLBCLs that express high levels of PDE4B,8 whereas PDE4 inhibitors restored glucocorticoid sensitivity and reduced tumor burden in in vivo preclinical models of human lymphoma.8 In these studies, the effects of PDE4 on glucocorticoid sensitivity were associated with modulation of PI3K/AKT signals.8 These data informed the design of a first-in-cancer clinical trial of the PDE4 inhibitor roflumilast (FDA-approved for severe chronic obstructive pulmonary disease). In this single-arm, pharmacokinetics and pharmacodynamics phase Ib study (clinicaltrials.gov identifier NCT01888952), the combination of roflumilast with prednisone was ...
Fibrotic diseases are characterized by the accumulation of extracellular matrix together with distortion and disruption of tissue architecture. Phosphodiesterase (PDE)4 inhibitors, by preventing the breakdown of cAMP, can inhibit fibroblast functions and may be able to mitigate tissue remodeling. Transforming growth factor (TGF)-β1, a mediator of fibrosis, can potentially modulate cAMP by altering PGE2 metabolism. The present study assessed whether PDE4 inhibitors functionally antagonize the profibrotic activity of fibroblasts stimulated by TGF-β1. The PDE4 inhibitors roflumilast and rolipram both inhibited fibroblast-mediated contraction of three-dimensional collagen gels and fibroblast chemotaxis toward fibronectin in the widely studied human fetal lung fibroblast strain HFL-1 and several strains of fibroblasts from adult human lung. Roflumilast was ~10-fold more potent than rolipram. There was a trend for PDE4 inhibitors to inhibit more in the presence of TGF-β1 (0.05 , P , 0.08). The ...
immune Uncategorized AIbZIP, roflumilast Dopachrome tautomerase (Dct) is a sort I membrane protein and an important regulatory enzyme that takes on a pivotal part in the biosynthesis of melanin and in the quick metabolism of its toxic intermediates. have a remarkably 28-collapse lower Dct activity. Homology modelling of the active site of Dct suggests that the mutation [R194Q (Arg194?Gln)] is located in the active site and may alter the ability of the enzyme to transform the substrate. Transmembrane prediction methods indicate the mutation [G486R (Gly486?Arg)] may result in the sliding of the transmembrane website for the N-terminus therefore interfering with Dct function. Chemical analysis showed that both Dct mutations increase pheomelanin and reduce eumelanin produced by melanocytes in tradition. Therefore the enzymatic activity of Dct may play a role in determining whether Roflumilast the eumelanin Roflumilast or pheomelanin pathway is preferred for pigment biosynthesis. (((gene result in ...
To determine the maximum-tolerated dose (MTD) of BKM120 when administered orally in combination with daily bicalutamide and LH-RH agonists to men with non
Daxas: Roflumilast belongs to the class of medications called phosphodiesterase 4 (PDE4) inhibitors. It is used along with a bronchodilator (e.g., salbutamol) to treat severe chronic obstructive pulmonary disease (COPD) with chronic cough and sputum (mucous) in adults who have frequent flare-ups. Roflumilast works by reducing inflammation in the lungs.
Katadolon Forte (Flupirtine, Flupirtinum) muscle relaxant, neuroprotective, analgesic central. Analgesic central action. It is a selective activator of neuronal potassium channels. Not applicable to opioids, it does not cause dependency and addiction.
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Chronic Obstructive Pulmonary Disease (COPD) exacerbations are a considerable reason for increased morbidity and mortality in patients. Infections with influenza virus (H1N1), respiratory syncytial virus (RSV) or nontypeable Haemophilus influenzae (NTHi) are important triggers of exacerbations. To date, no treatments are available which can stop the progression of COPD. Novel approaches are urgently needed. Pre-clinical models of the disease are crucial for the development of novel therapeutic options. In order to establish pre-clinical models which mimic aspects of human COPD exacerbations, mice were exposed to cigarette smoke (CS) and additionally infected with H1N1, RSV and/or NTHi. Clinically relevant treatments such as the corticosteroids Fluticasone propionate and Dexamethasone, the phosphodiesterase-4 (PDE-4) inhibitor Roflumilast and the long-acting muscarinic receptor antagonist Tiotropium were tested in the established models. Furthermore, a novel treatment approach using antibodies ...
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ionization potentials of amino pyridines, Tetrahedron Lett., 1973, 3193. [all data] Steck and Ewing, 1948. Steck, E.A.; Ewing, ... Bickerton, J.; Pilcher, G.; Al-Takhin, G., Enthalpies of combustion of the three aminopyridines and the three cyanopyridines, J ... Kim, B.; Thantu, N.; Weber, P.M., High resolution photoelectron spectroscopy: The vibrational spectrum of the 2-aminopyridine ... Kobayashi, T.; Nagakura, S., Photoelectron spectra of aminopyridines and cyanopyridines, J. Electron Spectrosc. Relat. Phenom. ...
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3-Aminopyridine is an aminopyridine. It can be used in the synthesis of organic ligand 3-pyridylnicotinamide 3-Aminopyridine ... Allen, C. F. H.; Wolf, Calvin N. (1950). "3-Aminopyridine". Organic Syntheses. 30: 3. doi:10.15227/orgsyn.030.0003. ; ... 3-Aminopyridine can easily be absorbed through the skin. It is fatal if swallowed or absorbed through the skin. High ...
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  • It can be used in the synthesis of organic ligand 3-pyridylnicotinamide 3-Aminopyridine can be prepared by heating nicotinamide with sodium hypobromite which is in turn prepared in situ by the reaction of sodium hydroxide and bromine at 70 °C. 3-Aminopyridine can easily be absorbed through the skin. (wikipedia.org)
  • Herein we report the synthesis and evaluation of aminopyridine and aminopyrimidine analogs of SX-517 and SX-576, identifying (2-{(benzyl)[(5-boronic acid-2-pyridyl)methyl]amino}-5-pyrimidinyl)(4-fluorophenylamino)formaldehyde as a potent chemokine antagonist with improved aqueous solubility and oral bioavailability. (nih.gov)
  • This invention relates a sustained release oral dosage form of an aminopyridine pharmaceutical composition that can be used to treat individuals affected with neurological disorders wherein said pharmaceutical composition maximizes the therapeutic effect, while minimizing adverse side effects. (freepatentsonline.com)
  • Similarly, IA and ID antagonist 4-aminopyridine (4AP) has been shown, in in vivo and in vitro studies, to cause hyperexcitability and the development of seizure-like epileptiform discharges [ 15 - 23 ]. (omicsonline.org)
  • The clinical applications of aminopyridines and further miscellaneous actions of aminopyridines and related compounds are also considered. (elsevier.com)
  • Aminopyridines and Similarly Acting Drugs: Effects on Nerves, Muscles and Synapses presents the proceedings of a IUPHAR Satellite Symposium in conjunction with the eighth International Congress of Pharmacology held in Paris, France on July 27-29, 1981. (elsevier.com)
  • This study aims to determine whether 4-aminopyridine (4AP) can reduce attacks of ataxia in patients with episodic ataxia type 2 (EA2), a rare but often debilitating condition. (clinicaltrials.gov)
  • 4-Aminopyridine-2,6-Dicarboxylic Acid (CAS 2683-49-0) Market Research Report 2018 aims at providing comprehensive data on 4-aminopyridine-2,6-dicarboxylic acid market globally and regionally (Europe, Asia, North America, Latin America etc. (marketpublishers.com)
  • 4-Aminopyridine (4-AP) is a drug that is used to improve motor fatigue in patients suffering from multiple sclerosis (MS). Medication error can occur, as commercial preparation may not be available in some countries. (hindawi.com)
  • The drug 4-aminopyridine partially restores some sensory and motor functions in one-third of patients who have been paralyzed for months to years. (thefreedictionary.com)
  • 4-Aminopyridine (4-AP) is indicated for the improvement of walking speed and motor fatigue in multiple sclerosis (MS). An overdose in 4-AP can produce detrimental side effects. (hindawi.com)
  • and the effects of aminopyridines on the release of chemical transmitters. (elsevier.com)
  • and the effects of aminopyridines on the skeletal, smooth and cardiac muscle. (elsevier.com)
  • The effects of 4-aminopyridine (4AP) on the extracellularly recorded nerve terminal action potential (NTAP) and end-plate potential were studied at the frog neuromuscular junction. (aspetjournals.org)
  • Boronic acid-containing aminopyridine- and aminopyrimidinecarboxamide CXCR1/2 antagonists: Optimization of aqueous solubility and oral bioavailabil. (nih.gov)
  • Boronic acid-containing aminopyridine- and aminopyrimidinecarboxamide CXCR1/2 antagonists: Optimization of aqueous solubility and oral bioavailability. (nih.gov)
  • The dose of 4-aminopyridine will increase 10 mg / every 2 to 4 weeks until reaching the maximum dose proposed by weight ( maximum 1 mg / kg / d). (clinicaltrials.gov)