Specific tricyclic antidepressant binding sites in rat brain
Specific tricyclic antidepressant binding sites in rat brain
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大鼠脑中特定的三环类抗抑郁药结合位点
DOI：
10.1038/281148a0
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发表时间：
1979
期刊：
影响因子：
64.8
通讯作者：
S. Z. Langer
中科院分区：
文献类型：
--
作者：
R. Raisman;M. Briley;S. Z. Langer
苯二氮卓类药物1、2、阿片类药物3和抗精神病药物4等精神活性药物的高亲和力结合位点的发现为研究这些药物及其作用机制开辟了新的途径。尽管大多数三环类抗抑郁药抑制去甲肾上腺素和降钙素5的神经元摄取，但其作用机制仍不清楚。长期三环类抗抑郁药治疗后β受体敏感性的变化6，7表明它们调节去甲肾上腺素能神经传递。三环类抗抑郁药也直接作用于胆碱能受体8、组胺能受体9、α-肾上腺素能受体10和肾上腺素能受体11。然而，尚不清楚这些效应中的哪些（如果有的话）与主要抗抑郁作用有关，或者它们是否只是导致一些副作用。因此，我们调查的可能性，三环类抗抑郁药的特异性结合位点存在于中枢神经系统。到目前为止，使用3H标记的三环类抗抑郁药的结合研究仅检测到与组胺能H2和胆碱能毒蕈碱受体12的结合以及低亲和力结合13。我们在这里展示了一个人口的特定的高亲和力结合位点的3H-丙咪嗪的脑细胞膜，这可能是负责这些药物的抗抑郁作用。
The discovery of high-affinity binding sites for psychoactive drugs such as benzodiazepines1,2, opiates3 and neuroleptics4 has opened up new approaches to the study of these drugs and their mechanisms of action. Although most tricyclic antidepressants inhibit neuronal uptake of noradrenaline and serotonin5, their mechanism of action remains unclear. Changes in the sensitivity of the β-receptor after chronic tricyclic antidepressant treatment6,7 suggest that they modulate noradrenergic neuro-transmission. Tricyclic antidepressants also act directly on cholinergic8, histaminergic9, α-adrenergic10 and serotonergic11 receptors. It is not clear, however, which, if any, of these effects are related to the primary antidepressant effect or whether they are simply responsible for some of the side effects. We have thus investigated the possibility that specific binding sites for tricyclic antidepressants exist in the central nervous system. So far, binding studies using 3H-labelled tricyclic antidepressant drugs have only detected binding to histaminergic H2 and cholinergic muscarinic receptors12 and low-affinity binding13. We demonstrate here a population of specific high-affinity binding sites for 3H-imipramine on brain membranes which may be responsible for the antidepressant effects of these drugs.
新生儿 6-羟基多巴胺治疗后脑部 β-肾上腺素能受体的发育。
影响因子：
3.8
作者：
Lorton,D;Bartolome,J;Slotkin,TA;Davis,JN
通讯作者：
Davis,JN