title: SR 120819A, an orally-active and selective neuropeptide Y Y1 receptor antagonist.
abstract: An orally-active antagonist of neuropeptide Y (NPY) Y1 receptors, SR 120819A, has been characterized. This compound displays highly selective and competitive affinity for rat, guinea-pig and human (Ki = 15 nM) NPY Y1 receptors. In vitro, SR 120819A blocks the inhibitory effect of NPY on adenylyl cyclase activity in human SK-N-MC cells and that of the selective Y1 agonist, [Leu31,Pro34]NPY, on rabbit vas deferens contraction (pA2 = 7.20 +/- 0.07). In vivo, by intravenous route, this compound acts as an antagonist in anesthetized guinea-pigs and, notably, after oral administration, SR 120819A counteracts the pressor response of [Leu31,Pro34]NPY (5 micrograms/kg i.v.) with a long duration of action (> 4 h at 5 mg/kg p.o.). Thus, SR 120819A is the first orally-effective NPY Y1 receptor antagonist yet described. It could be a useful tool for exploring the role of NPY and the therapeutic relevance of an antagonist at NPY Y1 receptors.
authors.affiliation: Sanofi Recherche, Toulouse, France.
authors.forename: C
authors.initials: C
authors.lastname: Serradeil-Le Gal
authors.forename: G
authors.initials: G
authors.lastname: Valette
authors.forename: P E
authors.initials: PE
authors.lastname: Rouby
authors.forename: A
authors.initials: A
authors.lastname: Pellet
authors.forename: F
authors.initials: F
authors.lastname: Oury-Donat
authors.forename: G
authors.initials: G
authors.lastname: Brossard
authors.forename: L
authors.initials: L
authors.lastname: Lespy
authors.forename: E
authors.initials: E
authors.lastname: Marty
authors.forename: G
authors.initials: G
authors.lastname: Neliat
authors.forename: P
authors.initials: P
authors.lastname: de Cointet
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D002460:Cell Line; D004558:Electric Stimulation; D006168:Guinea Pigs; D006801:Humans; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009281:Naphthalenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011759:Pyrrolidines; D011817:Rabbits; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D014649:Vas Deferens / Q000502:physiology
chemical_list: D009281:Naphthalenes; D009478:Neuropeptide Y; D011759:Pyrrolidines; D017476:Receptors, Neuropeptide Y; C093150:SR 120819A; D010649:Phenylalanine; D000262:Adenylyl Cyclases