Neuropharmacological characterization of SR 140333, a non peptide antagonist of NK1 receptors
Autor: | J. Souilhac, J.C. Brelière, R. Calassi, X. Emonds-Alt, Philippe Soubrie, G. Le Fur, Jeanne Maruani, Christiane Gueudet, M. Jung, M. Poncelet, M.C. Barnouin |
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Rok vydání: | 1994 |
Předmět: |
Central Nervous System
Male Agonist Quinuclidines medicine.drug_class Stereochemistry Substance P Pharmacology Cellular and Molecular Neuroscience chemistry.chemical_compound Neurokinin-1 Receptor Antagonists Piperidines medicine Animals Receptor Behavior Animal Chemistry Antagonist Stereoisomerism Scratching Rats Apomorphine Mechanism of action NK1 receptor antagonist medicine.symptom Salivation medicine.drug |
Zdroj: | Neuropharmacology. 33:167-179 |
ISSN: | 0028-3908 |
Popis: | SR 140333 (1-2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)piperidin-3-yl]ethyl-4-phenyl -1-azonia-bicyclo[2.2.2]octane, chloride), a potent non peptide ligand of the substance P (SP) NK1 receptor subtype with high affinity for NK1 receptors from both rat cortical membranes and human IM9 cells (Ki = 0.02 nM and 0.01 nM, respectively) was studied in vivo on various effects induced by NK1 agonists in rats and mice. SR 140333 given intraperitoneally (i.p.) in mice antagonized dose-dependently and in a stereoselective manner the scratching responses induced by intracerebroventricular SP and septide (ID50 = 0.73 and 0.08 mg/kg, respectively) and the turning behavior elicited by intrastriatal SP and septide (ID50 = 0.07 and 0.06 mg/kg, respectively). This compound had little effect on the scratching responses and the turning behavior elicited by [Sar9, Met(O2)11]-SP. When SR 140333 was coadministered with the peptide agonist, the compound reduced the scratching responses elicited by SP, [Sar9, Met(O2)11]-SP and septide injected intrathecally (i.t.) in mice (ID50 = 72.0, 64.3 and 52.5 ng i.t., respectively). SR 140333 antagonized the salivation induced by SP, [Sar9, Met(O2)11]-SP and septide in rats (ID50 =0.13, 0.18 and 0.09 mg/kg i.p., respectively). SR 140333 abolished the facilitation of the tail-flick reflex induced by noxious heat in rats (total reversal at 0.06 mg/kg, i.p.). This compound was also found to inhibit the turning behavior induced by intrastriatal apomorphine in mice (ID50 = 0.1 mg/kg, i.p.). In conclusion, these results indicate that SR 140333 behaves as a potent, selective and centrally active NK1 receptor antagonist. |
Databáze: | OpenAIRE |
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