谷氨酸N-甲基-D-天冬氨酸受体拮抗剂的抗抑郁作用研究进展

Research advances in anti-depression of glutamic acid N-methyl-D-aspartate receptor antagonists

谷氨酸是脑内主要的兴奋性神经递质,谷氨酸能神经元是构成中枢神经网络的主神经元,其数量超过脑内神经元总数的1/2。虽然中枢单胺类神经系统功能紊乱导致抑郁发生的假说已为大多数人所接受,但有证据表明谷氨酸类神经递质同样在抑郁发生中扮演着重要的角色。谷氨酸与抑郁症发生的相关确切机制还不清楚,但是研究发现谷氨酸能神经异常主要是通过谷氨酸N-甲基-D-天冬氨酸(NMDA)受体介导的。临床前研究及临床研究表明氯胺酮和利鲁唑等谷氨酸NMDA受体拮抗剂具有抗抑郁作用,提示治疗抑郁的新靶点,并需要更多样本量的随机对照试验进行验证。

Glutamic acid is the major central nervous system excitatory neurotransmitter found in more than 50%of synapses.While monoamines have been historically emphasized as causal factors in depression, evidences show that glutamate neurotransmission plays an important role.The exact mechanism by which glutamate may contribute towards depressive symptoms is unclear,but recent researches suggest that glutamatergic dysregulation is mediated via glutamate N-methyl-D）-aspartate（NMDA） receptors.Preclinical data,as well as several clinical studies,have indicated that NMDA receptor antagonists such as ketamine and riluzole have an anti-depressant effect,showing potential new targets for anti-depressant research.Larger controlled studies in the treatment of depression are warranted.