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SR120819A, an orally‐active and selective neuropeptide Y Y1 receptor antagonist
Author(s) -
Serradeil-Le Gal Claudine,
Valette Gérard,
Rouby Pierre-Eric,
Pellet Alain,
Oury-Donat Florence,
Brossard Gabrielle,
Lespy Liliane,
Marty Eléonore,
Neliat Gervais,
de Cointet Paul,
Maffrand Jean-Pierre,
Le Fur Gérard
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00230-7
Subject(s) - antagonist , orally active , neuropeptide y receptor , neuropeptide , chemistry , pharmacology , receptor antagonist , receptor , endocrinology , medicine , biology , oral administration , biochemistry
An orally‐active antagonist of neuropeptide Y (NPY) Y 1 receptors, SR 120819A, has been characterized. This compound displays highly selective and competitive affinity for rat, guinea‐pig and human ( K i = 15 nM) NPY Y 1 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 Y 1 agonist, [Leu 31 ,Pro 34 ]NPY, on rabbit vas deferens contraction (pA 2 = 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 [Leu 31 ,Pro 34 ]NPY (5 μg/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 Y 1 receptor antagonist yet descrobed. It could be a useful tool for exploring the role of NPY and the therapeutic relevance of an antagonist at NPY Y 1 receptors.