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NMDA受体拮抗剂

维基百科,自由的百科全书

NMDA受体拮抗剂(NMDA receptor antagonists)是一类能够对N-甲基-D-天門冬胺酸受體起拮抗或抑制作用的药物,通常被用于动物与人类作麻醉剂,由其诱导的麻醉状态称为解离性麻醉。

氯胺酮,最流行的NMDA受体拮抗剂之一

有几种合成阿片类药物具有NMDA受体拮抗剂之作用,如哌替啶左旋嗎汎美沙酮右丙氧吩曲马多酮贝米酮替安肽。一些NMDA受体拮抗剂,如氯胺酮右美沙芬苯環利定甲氧西他明氧化亚氮,有时因其具有解离、致幻与兴奋的主观体验,而被用于娱乐。当其用于娱乐时,归类为解离型药物

用途与效果

NMDA受体拮抗剂会诱发一种被称之为解离性麻醉的状态,特征有催眠失忆镇痛[1]氯胺酮呼吸血液循环的抑制作用小于其他麻醉剂,因而成为病史不明的急诊病人与治疗烧伤病人的首选麻醉剂。[2][3]右啡烷是世界上最常用的镇咳药之一[4]右美沙芬之代谢物,也是一种已知的NMDA受体拮抗剂。

许多不良症状都与NMDA受体功能低下有关。如,伴随大脑衰老导致的NMDA受体功能减退,或是造成与衰老有关的记忆力缺陷的部分原因。[5]精神分裂症也可能与不规则的NMDA受体功能有关(精神分裂症之谷氨酸假说),[6]并且进一步根据“犬尿酸假说”,另一种NMDA受体拮抗剂,犬尿喹啉酸含量的增加或会加重精神分裂症的症状。[7]

NMDA受体拮抗剂可以诱发“拟精神病”,即类似精神病之症状,还有以下副作用,包括幻觉、偏执性妄想、混乱、难以集中注意力、激动、情绪改变、噩梦[8]、紧张症[9]、共济失调[10]、麻醉[11]以及学习和记忆障碍。[12]由于这些“拟精神病”作用,NMDA受体拮抗剂,特别是苯环利定氯胺酮右美沙芬即被用作娱乐性药物。在亚麻醉剂量下,这些药物具有轻微的刺激作用,较大剂量时,诱发解离和幻觉,但这些作用及其强度因药物而异。[13]

大多数NMDA受体拮抗剂都会在肝脏中代谢,[14][15]频繁使用便会增加耐受,使肝脏更快清除血液中的NMDA受体拮抗剂。[16]

NMDA受体拮抗剂也在作为抗抑郁剂,处于研究之中。氯胺酮被证明于临床环境中,给药后可产生长效抗抑郁效果。2019年,氯胺酮的一种NMDA受体拮抗剂对映体esketamine于美国批准用作抗抑郁药。[17]2022年,FDA批准Auvelity用于治疗抑郁症,一种含有右美沙芬的复方药物。

参考文献

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