The alpha 1-adrenoceptor agonist, SDZ NVI-085, behaves as a potent, competitive antagonist of 5-hydroxytryptamine-induced contraction of rat aorta.

In this study we investigated the actions of SDZ NVI-085 ((-)-(4aR,10aR)-3,4,4a,5,10,10a-hexahydro-6-methoxy-4-methyl -9-(methylthio)-2H- naphth[2,3-b)-1,4-oxazine hydrogen malonate), previously classified and employed as a selective alpha 1-adrenoceptor agonist, in the rat isolated aorta assay. It was shown that, in addition to its alpha 1-adrenoceptor agonistic action, SDZ NVI-085 behaves as a competitive antagonist of 5-hydroxytryptamine (5-HT)-induced contraction of rat aorta (pKB = 8.13 +/- 0.08). The structurally related alpha 1-adrenoceptor agonist, SK & F 89748-A (l-1,2,3,4-tetrahydro-8-methoxy-5-(methylthio)-2-naphthalenamine hydrochloride), produced inhibition of the 5-HT response only at the highest concentration tested (1 microM) with an associated pA2 value of 6.0 +/- 0.1. These findings suggest that the affinity of SDZ NVI-085 for 5-HT2 receptors is considerably higher than for alpha 1-adrenoceptors, which may have implications for its use as a pharmacological tool.