Koyuncuoğlu H, Dizdar Y, Aricioğlu F, Sayin U
Istanbul Medical Faculty, Department of Pharmacology and Clinical Pharmacology, Capa, Türkey.
Pharmacol Biochem Behav. 1992 Oct;43(2):487-90. doi: 10.1016/0091-3057(92)90181-e.
It has previously been reported that the noncompetitive NMDA receptor antagonists ketamine and dextromethorphan suppressed the naloxone-induced morphine abstinence syndrome. In addition, the previous blockade by ketamine and dextromethorphan of NMDA receptors has been shown to intensify the naloxone-elicited morphine abstinence syndrome. On the basis of this information, another noncompetitive NMDA receptor antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo-a,d-cyclohepten-5,10-imine maleate (MK 801), was administered to rats in which two morphine-containing (75 x 2 morphine base) pellets had been implanted. The naloxone-precipitated abstinence syndrome in rats injected with 0.3 mg/kg MK 801 36 h after pellet implantation was found significantly more intense than controls whereas the abstinence syndrome in rats that received 0.1 mg/kg MK 801 before naloxone injection was less intense. The intensification by MK 801 given 36 h following pellet implantation was attributed to the further increase in upregulation and supersensitivity of NMDA receptors caused by morphine. The attenuation was explained by the blockade by MK 801 of NMDA receptors as occurred in the case of ketamine and dextromethorphan.
此前有报道称，非竞争性NMDA受体拮抗剂氯胺酮和右美沙芬可抑制纳洛酮诱发的吗啡戒断综合征。此外，氯胺酮和右美沙芬此前对NMDA受体的阻断已被证明会加剧纳洛酮诱发的吗啡戒断综合征。基于此信息，给植入了两个含吗啡（75×2吗啡碱）药丸的大鼠施用了另一种非竞争性NMDA受体拮抗剂，马来酸（+）-5-甲基-10,11-二氢-5H-二苯并-a,d-环庚烯-5,10-亚胺（MK 801）。发现在药丸植入后36小时注射0.3mg/kg MK 801的大鼠中，纳洛酮诱发的戒断综合征明显比对照组更强烈，而在纳洛酮注射前接受0.1mg/kg MK 801的大鼠中，戒断综合征则较弱。药丸植入后36小时给予MK 801导致的增强作用归因于吗啡引起的NMDA受体上调和超敏反应的进一步增加。这种减弱现象是由于MK 801对NMDA受体的阻断作用，就像氯胺酮和右美沙芬的情况一样。
