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)-2 H-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 (pK(B) = 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 mu M) with an associated pA(2) 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.