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.
Van der Graaf
P H
PH
Department of Pharmacology, Erasmus University Rotterdam, Netherlands.
Apaydin
S
S
Saxena
P R
PR
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001667:Binding, Competitive; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010078:Oxazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D001952:Bridged-Ring Compounds; D010078:Oxazines; D013764:Tetrahydronaphthalenes; C074349:SDZ NVI-085; D012701:Serotonin; C039140:SK&F 89748