Selective alpha-adrenoceptor blocking actions of a new derivative of 2-halogenotheylamine: 6-(2-bromoethyl)-10,11-methylenedioxy-5,6,7,8-tetrahydrodibenz[c,e]azocine.
A new compound, 6-(2-bromoethyl)-10,11-methylenedioxy-5,6,7,8-tetrahydrodibenz [c,e] azocine (DA-VIII-MBr) was found to have a more selective alpha-adrenergic blocking action than dibenamine or phenoxybenzamine. From dose-response curves for adrenaline and 5-hydroxytryptamine (5-HT) obtained in strips of rat aorta before and after incubation with each of the three blocking agents, the fractions of receptors remaining active for adrenaline and 5-HT, respectively, were estimated. After blockade with DA-VIII-MBr the receptors for adrenaline were blocked considerably, but those for 5-HT were little affected. Dibenamine blocked the receptors to adrenaline and 5-HT almost equally. The effective dose of phenoxybenzamine for adrenaline receptors was less than one hundredth that of dibenamine or DA-VIII-MBr, but specificity for these receptors was intermediate between those of dibenamine and DA-VIII-MBr. The structure of DA-VIII-MBr is an analog of apogalanthamine and its nitrogen atom bears the 2-halogenoethylamine group in part of an eight membered ring.
D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001392:Azocines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003983:Dibenzylchlorethamine / Q000494:pharmacology; D004148:Dioxolanes / Q000494:pharmacology; D004347:Drug Interactions; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D013116:Spinal Cord / Q000502:physiology; D014649:Vas Deferens / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D001392:Azocines; D004148:Dioxolanes; D010643:Phenoxybenzamine; D012701:Serotonin; D003983:Dibenzylchlorethamine; D006632:Histamine; D004837:Epinephrine