Kosten T A, DeCaprio J L, Rosen M I
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
Neuropsychopharmacology. 1995 Dec;13(4):323-33. doi: 10.1016/0893-133X(95)00065-L.
Recent studies indicate that an N-methyl-D-aspartate (NMDA) receptor system in the rostral medulla is involved in opiate withdrawal. Although NMDA antagonists attenuate naloxone-precipitated opiate withdrawal, they can cause phencyclidine (PCP)like effects that contraindicate clinical use. Because NMDA channels contain sites for the glutamate coagonist, glycine, we assessed the effects of glycinergic agents on naloxone-precipitated opiate withdrawal in rats. The putative antagonist, felbamate (100, 300 mg/kg), attenuated overall withdrawal severity in a dose-related manner and reduced occurrences of chews, teeth chatters, and penile grooming. The partial agonist, D-cycloserine (3, 10 mg/kg), attenuated withdrawal severity, but not in a dose-related manner. Conversely, the low dose of the partial agonist, (+/-)-HA-966 (3, 10 mg/kg), heightened the occurrences of some withdrawal signs. These results support a role for glycine in opiate withdrawal and suggest that these agents, which do not cause PCPlike effects, may be potential treatment for agents for opiate detoxification.
最近的研究表明，延髓头端的N-甲基-D-天冬氨酸（NMDA）受体系统与阿片类药物戒断有关。虽然NMDA拮抗剂可减轻纳洛酮诱发的阿片类药物戒断反应，但它们会产生类似苯环己哌啶（PCP）的效应，这限制了其临床应用。由于NMDA通道含有谷氨酸协同激动剂甘氨酸的结合位点，我们评估了甘氨酸能药物对大鼠纳洛酮诱发的阿片类药物戒断反应的影响。推测的拮抗剂非氨酯（100、300毫克/千克）以剂量相关的方式减轻了总体戒断严重程度，并减少了咀嚼、牙齿打颤和阴茎梳理行为的发生。部分激动剂D-环丝氨酸（3、10毫克/千克）减轻了戒断严重程度，但并非呈剂量相关。相反，低剂量的部分激动剂（±）-HA-966（3、10毫克/千克）增加了一些戒断症状的发生。这些结果支持了甘氨酸在阿片类药物戒断中的作用，并表明这些不会产生类似PCP效应的药物可能是阿片类药物解毒的潜在治疗药物。
