NMDA受體拮抗劑
NMDA受體拮抗劑（NMDA receptor antagonists）是一類能夠對N-甲基-D-天門冬胺酸受體起拮抗或抑制作用的藥物，通常被用於動物與人類作麻醉劑，由其誘導的麻醉狀態稱為解離性麻醉。
有幾種合成阿片類藥物具有NMDA受體拮抗劑之作用，如哌替啶、左旋嗎汎、美沙酮、右丙氧吩、曲馬多、酮貝米酮和替安肽。一些NMDA受體拮抗劑，如氯胺酮、右美沙芬、苯環利定、甲氧西他明和氧化亞氮，有時因其具有解離、致幻與興奮的主觀體驗，而被用於娛樂。當其用於娛樂時，歸類為解離型藥物。
用途與效果 編輯
NMDA受體拮抗劑會誘發一種被稱之為解離性麻醉的狀態，特徵有催眠、失憶和鎮痛。[1]氯胺酮對呼吸和血液循環的抑制作用小於其他麻醉劑，因而成為病史不明的急診病人與治療燒傷病人的首選麻醉劑。[2][3]右啡烷是世界上最常用的鎮咳藥之一[4]的右美沙芬之代謝物，也是一種已知的NMDA受體拮抗劑。
許多不良症狀都與NMDA受體功能低下有關。如，伴隨大腦衰老導致的NMDA受體功能減退，或是造成與衰老有關的記憶力缺陷的部分原因。[5]精神分裂症也可能與不規則的NMDA受體功能有關（精神分裂症之穀氨酸假說），[6]並且進一步根據「犬尿酸假說」，另一種NMDA受體拮抗劑，犬尿喹啉酸含量的增加或會加重精神分裂症的症狀。[7]
NMDA受體拮抗劑可以誘發「擬精神病」，即類似精神病之症狀，還有以下副作用，包括幻覺、偏執性妄想、混亂、難以集中注意力、激動、情緒改變、噩夢[8]、緊張症[9]、共濟失調[10]、麻醉[11]以及學習和記憶障礙。[12]由於這些「擬精神病」作用，NMDA受體拮抗劑，特別是苯環利定、氯胺酮和右美沙芬即被用作娛樂性藥物。在亞麻醉劑量下，這些藥物具有輕微的刺激作用，較大劑量時，誘發解離和幻覺，但這些作用及其強度因藥物而異。[13]
大多數NMDA受體拮抗劑都會在肝臟中代謝，[14][15]頻繁使用便會增加耐受，使肝臟更快清除血液中的NMDA受體拮抗劑。[16]
NMDA受體拮抗劑也在作為抗抑鬱劑，處於研究之中。氯胺酮被證明於臨床環境中，給藥後可產生長效抗抑鬱效果。2019年，氯胺酮的一種NMDA受體拮抗劑對映體esketamine於美國批准用作抗抑鬱藥。[17]2022年，FDA批准Auvelity用於治療抑鬱症，一種含有右美沙芬的複方藥物。
參考文獻 編輯
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