SDZ NVI 085, an α1A-adrenoceptor agonist with 5-HT2A receptor antagonist properties

Abstract (±)-SDZ NVI 085 (3,4,4 a 5,10,10 a -hexahydro-6-methoxy-4-methyl-9-methylthio-2 H -naphth[2,3- b ]-1,4-oxazine hydrochloride), an α 1 -adrenoceptor agonist, produced a concentration-dependent relaxation (pIC 50 of 7.2 ± 0.1) in the isolated caudal artery of rat precontracted with serotonin (5-hydroxytryptamine, 5-HT, 1 μM). (±)-SDZ NVI 085 had no effect upon caudal arteries precontracted with vasopressin or U46619 (9,11-dideoxy-11α,9α-epoxymethano-prostaglandin F 2α ). 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 pA 2 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-HT 2 receptor antagonist) toward 5-HT-induced contractions. It is concluded that (±)-SDZ NVI 085 behaves as a reversible competitive 5-HT 2A receptor antagonist, a property which may be of importance regarding its pharmacological effects in vivo.