IS PINDOLOL A MIXED AGONIST-ANTAGONIST AT CENTRAL SEROTONIN (5-HT) RECEPTORS
IS PINDOLOL A MIXED AGONIST-ANTAGONIST AT CENTRAL SEROTONIN (5-HT) RECEPTORS
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DOI：
10.1016/0014-2999(86)90344-4
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发表时间：
1986-09-23
影响因子：
5
通讯作者：
CARLSSON, A
中科院分区：
文献类型：
--
作者：
HJORTH, S;CARLSSON, A
非选择性的β-用在体生物化学方法研究了肾上腺素能阻断剂吲哚洛尔对大鼠中枢单胺能神经传递的影响。结果表明，（-）-吲哚洛尔可明显、选择性、剂量依赖性和立体特异性地降低脑5-HT合成速率。合成减少并不伴随着组织色氨酸水平的任何变化，并且不能通过利血平消耗单胺储存来防止。此外，在未经预处理的动物中，（-）-而不是（+）-吲哚洛尔（或β 1-和β 2-选择性肾上腺素受体拮抗剂美托洛尔、倍他洛尔和ICI 118，551）降低了5-HIAA水平和5-HIAA/5-HT比率，而两种对映异构体均未改变5-HT或NA或DA及其代谢物的浓度。这表明，（-）-吲哚洛尔的这些作用可能是由于直接刺激中枢神经系统的5-HT受体。在文献数据的内容中讨论了该化合物的作用，表明其能够作为5-HT受体活化的某些其他方面的拮抗剂。考虑的可能性是，除了它的β-（-）-吲哚洛尔是中枢5-HT受体的混合激动剂-拮抗剂。
The effects of the non-selective .beta.-adrenergic blocking agent pindolol upon central monoaminergic neurotransmission in rats were studied by means of in vivo biochemical methods. It was found that (-)-pindolol elicited a clearcut, selective, dose-dependent and stereospecific reduction of brain 5-HT synthesis rate. The synthesis reduction was not accompanied by any change in the tissue tryptophan level and could not be prevented by depleting the monoamine stores by means of reserpine. Furthermore, in non-pretreated animals , (-)- but not (+)-pindolol (or the .beta.1- and .beta.2-selective adrenoceptor antagonists metoprolol, betaxolol and ICI 118,551) decreased the 5-HIAA level and the 5-HIAA/5-HT ratio while neither enantiomer altered the concentrations of 5-HT or NA, or DA and its metabolites. It is suggested that these effects of(-)-pindolol may be due to direct stimulation of 5-HT receptors in the CNS. The action of the compound is discussed within the content of literature data indicating its ability to act as an antagonist of certain other aspects of 5-HT receptor activation. The possibility is considered, that, in addition to its .beta.-adrenergic properties, (-)-pindolol is a mixed agonist-antagonist at central 5-HT receptors.