NMDA受体拮抗剂

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。 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、酮贝米酮和替安肽。一些NMDA受体拮抗剂，如氯胺酮、右美沙芬、苯環利定、甲氧西他明和氧化亚氮，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。 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、失忆和镇痛。氯胺酮对呼吸和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。右啡烷是世界上最常用的镇咳药之一的右美沙芬之代谢物，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。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），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。 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、紧张症、共济失调、麻醉以及学习和记忆障碍。由于这些“拟精神病”作用，NMDA受体拮抗剂，特别是苯环利定、氯胺酮和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。 大多数NMDA受体拮抗剂都会在肝脏中代谢，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。 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。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。 Pender JW. Dissociative anesthesia. JAMA. February 1971, 215 (7): 1126–30. PMC 1518731 . PMID 5107596. doi:10.1001/jama.1971.03180200050011.  Ceber M, Salihoglu T. Ketamine may be the first choice for anesthesia in burn patients. Journal of Burn Care & Research. 2006, 27 (5): 760–2. PMID 16998413. doi:10.1097/01.BCR.0000238091.41737.7C.  Heshmati F, Zeinali MB, Noroozinia H, Abbacivash R, Mahoori A. Use of ketamine in severe status asthmaticus in intensive care unit. Iranian Journal of Allergy, Asthma, and Immunology. December 2003, 2 (4): 175–80. PMID 17301376.  Equinozzi R, Robuschi M. Comparative efficacy and tolerability of pholcodine and dextromethorphan in the management of patients with acute, non-productive cough : a randomized, double-blind, multicenter study. Treatments in Respiratory Medicine. 2006, 5 (6): 509–13. PMID 17154678. S2CID 58323644. doi:10.2165/00151829-200605060-00014.  Newcomer JW, Krystal JH. NMDA receptor regulation of memory and behavior in humans. Hippocampus. 2001, 11 (5): 529–42. PMID 11732706. S2CID 32617915. doi:10.1002/hipo.1069.  Lipina T, Labrie V, Weiner I, Roder J. Modulators of the glycine site on NMDA receptors, D-serine and ALX 5407, display similar beneficial effects to clozapine in mouse models of schizophrenia. Psychopharmacology. April 2005, 179 (1): 54–67. PMID 15759151. S2CID 10858756. doi:10.1007/s00213-005-2210-x.  Erhardt S, Schwieler L, Nilsson L, Linderholm K, Engberg G. The kynurenic acid hypothesis of schizophrenia. Physiology & Behavior. September 2007, 92 (1–2): 203–9. PMID 17573079. S2CID 46156877. doi:10.1016/j.physbeh.2007.05.025.  Muir KW, Lees KR. Clinical experience with excitatory amino acid antagonist drugs. Stroke. March 1995, 26 (3): 503–13 [2023-10-01]. PMID 7886734. doi:10.1161/01.STR.26.3.503. （原始内容存档于2010-12-06）.  Aarts MM, Tymianski M. Novel treatment of excitotoxicity: targeted disruption of intracellular signalling from glutamate receptors. Biochemical Pharmacology. September 2003, 66 (6): 877–86. PMID 12963474. doi:10.1016/S0006-2952(03)00297-1.  Kim AH, Kerchner GA, Choi DW. Blocking Excitotoxicity. Marcoux FW, Choi DW (编). CNS Neuroprotection. New York: Springer. 2002: 3–36.  Kristensen JD, Svensson B, Gordh T. The NMDA-receptor antagonist CPP abolishes neurogenic 'wind-up pain' after intrathecal administration in humans. Pain. November 1992, 51 (2): 249–53. PMID 1484720. S2CID 37828325. doi:10.1016/0304-3959(92)90266-E.  Rockstroh S, Emre M, Tarral A, Pokorny R. Effects of the novel NMDA-receptor antagonist SDZ EAA 494 on memory and attention in humans. Psychopharmacology. April 1996, 124 (3): 261–6. PMID 8740048. S2CID 36727794. doi:10.1007/BF02246666.  Lim DK. Ketamine associated psychedelic effects and dependence. Singapore Medical Journal. January 2003, 44 (1): 31–4. PMID 12762561.  Chia YY, Liu K, Chow LH, Lee TY. The preoperative administration of intravenous dextromethorphan reduces postoperative morphine consumption. Anesthesia and Analgesia. September 1999, 89 (3): 748–52. PMID 10475318. doi:10.1097/00000539-199909000-00041 .  Kharasch ED, Labroo R. Metabolism of ketamine stereoisomers by human liver microsomes. Anesthesiology. December 1992, 77 (6): 1201–7. PMID 1466470. doi:10.1097/00000542-199212000-00022 .  Livingston A, Waterman AE. The development of tolerance to ketamine in rats and the significance of hepatic metabolism. British Journal of Pharmacology. September 1978, 64 (1): 63–9. PMC 1668251 . PMID 698482. doi:10.1111/j.1476-5381.1978.tb08641.x.  FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor's office or clinic. Food and Drug Administration. 24 March 2020 [2023-10-01]. （原始内容存档于2019-04-23）.