The 5-HT and alpha-adrenoceptor antagonist effect of four benzylisoquinoline alkaloids on rat aorta.
The action of four benzylisoquinoline alkaloids (two aporphines-glaucine and apomorphine, a benzylisoquinoline-papaverine and a bisbenzyltetrahydroisoquinoline-antioquine) on 5-HT-induced contraction in rat thoracic aorta has been examined and compared with that of the control drugs: ketanserin, nifedipine, prazosin and phentolamine. The relaxant action on 5-HT-induced contraction was contrasted with that on the contraction induced by noradrenaline and KCl. The results obtained with control drugs show that ketanserin has clear selectivity for 5-HT receptors, whereas prazosin and phentolamine have high selectivity for the alpha1-adrenoceptor and nifedipine seems to have a more potent effect on KCl-induced contraction than on that induced by 5-HT or noradrenaline. The contraction evoked by 5-HT (10 microM) was inhibited in a concentration-dependent manner by all the alkaloids. The order of potency was: papaverine = glaucine > apomorphine > antioquine. Papaverine had a non-specific relaxant action on 5-HT-, noradrenaline- and KCl-induced contraction, antioquine had a weak relaxant action on the agonist assays, and glaucine and apomorphine inhibited noradrenaline- and 5-HT-induced contraction more potently than they inhibited the K+-depolarized response. These results indicate that the aporphines assayed, S-glaucine and R-aporphine, had selective action against agonist (noradrenaline or 5-HT)-induced contraction rather than against KCl-depolarization of rat aorta. In contrast papaverine, a benzylisoquinoline alkaloid, relaxes all agents used non-selectively as could be expected from the lack of specificity that characterizes this alkaloid.
Catret
M
M
Departamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, Burjasot, Spain.
Ivorra
M D
MD
D'Ocón
M P
MP
Anselmi
E
E
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001058:Apomorphine / Q000494:pharmacology; D001060:Aporphines / Q000494:pharmacology; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010208:Papaverine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin
D000317:Adrenergic alpha-Antagonists; D000470:Alkaloids; D001060:Aporphines; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D018491:Dopamine Agonists; D007546:Isoquinolines; D010276:Parasympatholytics; D012701:Serotonin; C059733:antioquine; D010208:Papaverine; D001058:Apomorphine; C005004:glaucine