β-Carboline-3-carboxylic acid ethyl ester antagonizes diazepam activity
β-Carboline-3-carboxylic acid ethyl ester antagonizes diazepam activity
复制标题
β-咔啉-3-羧酸乙酯拮抗地西泮活性
作者：
S. Tenen;J. Hirsch
类似于阿片受体-脑啡肽区域的事件进展，第一个报告1-3苯二氮卓类药物在大脑中具有选择性和特异性的高亲和力结合部位，刺激了对可能在这些部位正常作用的内源性‘配体’或物质的研究4-9。10)，最近鉴定为β-Caroline-3-羧酸乙酯(βCEE)。他们报告说，这种物质在取代脑结合部位的~3H-地西潘方面非常有效，并提出β-Caroline-3-羧酸衍生物可能在一定程度上是大脑苯二氮卓受体的内源性配体。我们已经检查了几个合成的β-Caroline-3-羧酸类似物，现在提供了仅通过测试Braestrup等人描述的βCEE获得的数据。除了证实这些工作人员的观察结果，即这种化合物是脑组织中的一种有效的~3H-地西潘替代品外，我们的药理学数据还表明，βCEE的活性与地西潘相反，而不是相似。
Analogous to the progression of events in the opiate receptor–enkephalin area, the first reports1–3 that benzodiazepines have selective and specific high-affinity binding sites in brain have stimulated a search for the endogenous ‘ligand’ or substance that might normally act at these sites4–9. Braestrup and co-workers have extracted from human urine a γ-fraction (ref. 10) which they have recently11 identified as β-carboline-3-carboxylic acid ethyl ester (βCEE). They reported that this substance is extremely potent in displacing 3H-diazepam from brain binding sites and proposed that a β-carboline-3-carboxylic acid derivative might, in part, be the endogenous ligand for the brain benzodiazepine receptor. We have examined several synthetically derived β-carboline-3-carboxylic acid analogues and now present data obtained from testing only the βCEE described by Braestrup et al. In addition to confirming these workers' observation that this compound is a potent displacer of 3H-diazepam from brain tissue, our pharmacological data indicate that βCEE has activity that is opposite to, rather than similar to, that of diazepam.