Catret M, Ivorra M D, D'Ocón M P, Anselmi E
Departamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, Burjasot, Spain.
J Pharm Pharmacol. 1998 Mar;50(3):317-22. doi: 10.1111/j.2042-7158.1998.tb06867.x.
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.
研究了四种苄基异喹啉生物碱（两种阿朴啡类——青藤碱和阿扑吗啡，一种苄基异喹啉类——罂粟碱，以及一种双苄基四氢异喹啉类——抗疟喹）对大鼠胸主动脉5-羟色胺（5-HT）诱导收缩的作用，并与对照药物酮色林、硝苯地平、哌唑嗪和酚妥拉明进行了比较。将它们对5-HT诱导收缩的舒张作用与对去甲肾上腺素和氯化钾诱导收缩的作用进行了对比。对照药物的实验结果表明，酮色林对5-HT受体具有明显的选择性，而哌唑嗪和酚妥拉明对α1-肾上腺素受体具有高度选择性，硝苯地平对氯化钾诱导的收缩似乎比对5-HT或去甲肾上腺素诱导的收缩具有更强的作用。所有生物碱均以浓度依赖性方式抑制5-HT（10微摩尔）诱发的收缩。效力顺序为：罂粟碱 = 青藤碱 > 阿扑吗啡 > 抗疟喹。罂粟碱对5-HT、去甲肾上腺素和氯化钾诱导的收缩具有非特异性舒张作用，抗疟喹在激动剂试验中具有较弱的舒张作用，青藤碱和阿扑吗啡抑制去甲肾上腺素和5-HT诱导的收缩比抑制钾离子去极化反应更有效。这些结果表明，所检测的阿朴啡类，S-青藤碱和R-阿朴啡，对激动剂（去甲肾上腺素或5-HT）诱导的收缩具有选择性作用，而不是对大鼠主动脉的氯化钾去极化作用。相比之下，苄基异喹啉生物碱罂粟碱非选择性地舒张所有使用的药物，这正如该生物碱缺乏特异性所预期的那样。
