title: SDZ NVI 085, an alpha 1A-adrenoceptor agonist with 5-HT2A receptor antagonist properties.
abstract: (+/-)-SDZ NVI 085 (3,4,4a,5,10,10a-hexahydro-6-methoxy-4-methyl-9- methylthio-2H-naphth [2,3-b]-1,4-oxazine hydrochloride), an alpha 1-adrenoceptor agonist, produced a concentration-dependent relaxation (pIC50 of 7.2 +/- 0.1) in the isolated caudal artery of rat precontracted with serotonin (5-hydroxytryptamine, 5-HT, 1 microM). (+/-)- SDZ NVI 085 had no effect upon caudal arteries precontracted with vasopressin or U46619 (9,11-dideoxy-11 alpha, 9 alpha-epoxymethano-prostaglandin F2 alpha). In other studies, (+/-)-SDZ NVI 085 shifted 5-HT concentration-effect curves to the right, in a concentration-dependent manner, and Schild regression gave a pA2 estimate of 8.0 (slope of 1.0). Experiments using pharmacological resultant analysis indicated a syntopic interaction of (+/-)-SDZ NVI 085 with ketanserin (a 5-HT2 receptor antagonist) toward 5-HT-induced contractions. It is concluded that (+/-)-SDZ NVI 085 behaves as a reversible competitive 5-HT2A receptor antagonist, a property which may be of importance regarding its pharmacological effects in vivo.
authors.affiliation: Roche Bioscience, Palo Alto, CA 94304, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Lachnit
authors.forename: A P
authors.initials: AP
authors.lastname: Ford
authors.forename: D E
authors.initials: DE
authors.lastname: Clarke
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D019329:Idazoxan / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010078:Oxazines / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013623:Tail / Q000098:blood supply
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001952:Bridged-Ring Compounds; D010078:Oxazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C074349:SDZ NVI-085; D007650:Ketanserin; D011224:Prazosin; D019329:Idazoxan