三环类抗抑郁药阻断N-甲基-D-天冬氨酸受体：与锌的作用相似。
Tricyclic antidepressants block N-methyl-D-aspartate receptors: similarities to the action of zinc.
作者信息
Reynolds I J, Miller R J
机构信息
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60615.
出版信息
Br J Pharmacol. 1988 Sep;95(1):95-102. doi: 10.1111/j.1476-5381.1988.tb16552.x.
Abstract
- Using the radioligand [3H]-MK801, we have examined drug interactions with the phencyclidine recognition site of the N-methyl-D-aspartate receptor. 2. The tricyclic antidepressants desmethylimipramine and imipramine inhibited [3H]-MK801 binding with IC50 values of 7.4 and 22.5 microM, respectively. Other related tricyclic antidepressants and neuroleptics were also effective but less potent. 3. Desmethylimipramine, imipramine and chlorimipramine slowed the dissociation rate of [3H]-MK801 in a similar manner to Zn2+. Phencyclidine and related compounds had no effect on the dissociation rate of [3H]-MK801. 4. Desmethylimipramine, imipramine and ketamine also prevented the Ca2+ influx into cultured cortical neurones of the rat produced by N-methyl-D-aspartate. 5. As the actions of tricyclic antidepressants in this system are not competitive with respect to N-methyl-D-aspartate, glycine or MK-801, and as they slow the dissociation of [3H]-MK801, we conclude that tricyclic antidepressants may be acting at the Zn2+ recognition site on the N-methyl-D-aspartate receptor.
摘要
- 我们使用放射性配体[3H]-MK801，研究了药物与N-甲基-D-天冬氨酸受体苯环利定识别位点的相互作用。2. 三环类抗抑郁药去甲丙咪嗪和丙咪嗪抑制[3H]-MK801结合，IC50值分别为7.4和22.5微摩尔。其他相关的三环类抗抑郁药和抗精神病药也有效，但效力较低。3. 去甲丙咪嗪、丙咪嗪和氯米帕明以与Zn2+相似的方式减缓了[3H]-MK801的解离速率。苯环利定及相关化合物对[3H]-MK801的解离速率没有影响。4. 去甲丙咪嗪、丙咪嗪和氯胺酮也阻止了N-甲基-D-天冬氨酸引起的大鼠培养皮层神经元中的Ca2+内流。5. 由于三环类抗抑郁药在该系统中的作用对N-甲基-D-天冬氨酸、甘氨酸或MK-801不具有竞争性，并且它们减缓了[3H]-MK801的解离，我们得出结论，三环类抗抑郁药可能作用于N-甲基-D-天冬氨酸受体上的Zn2+识别位点。
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