Actions of serotonin antagonists on dog coronary artery.
Actions of serotonin antagonists on dog coronary artery.
复制标题
血清素拮抗剂对狗冠状动脉的作用。
DOI：
10.1016/0014-2999(82)90346-6
复制
发表时间：
1982
影响因子：
5
通讯作者：
J. Angus
中科院分区：
文献类型：
--
作者：
R. Brazenor;J. Angus
血小板释放的5-羟色胺可引起变异型心绞痛患者的冠状动脉痉挛。如果这一假设是正确的，没有收缩活性的5-羟色胺拮抗剂可能对这种形式的心绞痛有用。我们研究了5-羟色胺拮抗剂类药物对犬冠状动脉回旋支环段的体外作用。麦角胺、双氢麦角胺、溴隐亭、麦角乙脲、麦角新碱、酮色林、曲唑酮、赛庚啶和吡唑替芬引起5-羟色胺浓度-反应曲线的非竞争性拮抗作用。此外，酮色林，曲唑酮，溴隐亭和吡唑替芬抑制去甲肾上腺素反应的浓度类似于血清素拮抗作用所需的浓度。除酮色林、赛庚啶和吡唑替芬外，所有药物均表现出一定程度的内在收缩活性。麦角新碱竞争性地拮抗对5-羟色胺的反应，但也使冠状动脉收缩。缺乏沉默的竞争性5-羟色胺拮抗剂，排除了明确的特点，冠状动脉5-羟色胺受体在这个时候。然而，在冠状动脉中观察到的拮抗剂药物的活性特征与在其他血管组织中观察到的不同。在测试的药物中，酮色林可能是变异型心绞痛中最有用的，因为它是一种有效的5 HT拮抗剂，缺乏激动剂活性，并具有α-肾上腺素受体阻断活性。
Serotonin released from platelets may initiate coronary vasopasm in patients with variant angina. If this hypothesis is correct, serotonin antagonists without constrictor activity may be useful in this form of angina. We have investigated drugs classified as serotonin antagonists on dog circumflex coronary artery ring segments in vitro. Ergotamine, dihydroergotamine, bromocriptine, lisuride, ergometrine, ketanserin, trazodone, cyproheptadine and pizotifen caused non-competitive antagonism of serotonin concentration-response curves. In addition, ketanserin, trazodone, bromocriptine and pizotifen inhibited noradrenaline responses in concentrations similar to those required for serotonin antagonism. All drugs with the exception of ketanserin, cyproheptadine and pizotifen showed some degree of intrinsic constrictor activity. Methysergide antagonized responses to serotonin competitively but also constricted the coronary artery. The lack of a silent competitive serotonin antagonist precludes a definite characterization of coronary serotonin receptors at this time. However, the profile of activity observed for the antagonist drugs in the coronary artery differs from that seen in other vascular tissues. Of the drugs tested, ketanserin may be the most useful in variant angina since it is a potent 5HT antagonist, lacks agonist activity and has α-adrenoceptor blocking activity.