Erden B F, Ozdemirci S, Yildiran G, Utkan T, Gacar N, Ulak G
Department of Pharmacology, Kocaeli Medical Faculty, Derince, Turkey.
Pharmacol Biochem Behav. 1999 Mar;62(3):537-41. doi: 10.1016/s0091-3057(98)00175-0.
The effects of dextromethorphan (DM), a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptors, have been investigated on ethanol withdrawal signs in rats. Ethanol (7.2% v/v) was given to rats in a liquid diet for 16 days. DM (10, 20, and 40 mg/kg) and saline were injected intraperitoneally at the third hour of ethanol withdrawal. DM (40 mg/kg) and ethanol dependent saline were also administered to ethanol naive rats. DM (40 mg/kg) did not produce any significant change in locomotor activity in ethanol naive rats. The effects of DM on locomotor activity and total ethanol withdrawal score were evaluated at the fourth and sixth hours of ethanol withdrawal. DM inhibited locomotor hyperactivity at these periods. DM also reduced total ethanol withdrawal score from the fourth hour to the sixth hour, and it significantly decreased audiogenic seizures. Seizure susceptibility after chronic ethanol exposure may be dependent upon sensitization or upregulation of NMDA processes and NMDA receptors. Our results suggest that inhibition of NMDA receptors by DM alleviates signs of ethanol withdrawal.
右美沙芬（DM）是N-甲基-D-天冬氨酸（NMDA）受体的非竞争性拮抗剂，其对大鼠乙醇戒断症状的影响已得到研究。以含7.2%（体积/体积）乙醇的液体饲料喂养大鼠16天。在乙醇戒断的第3小时腹腔注射DM（10、20和40毫克/千克）和生理盐水。还对未接触过乙醇的大鼠给予DM（40毫克/千克）和依赖乙醇的生理盐水。DM（40毫克/千克）对未接触过乙醇的大鼠的运动活性未产生任何显著变化。在乙醇戒断的第4小时和第6小时评估DM对运动活性和乙醇戒断总评分的影响。在此期间，DM抑制了运动亢进。DM还使从第4小时到第6小时的乙醇戒断总评分降低，并且显著减少了听源性惊厥。长期乙醇暴露后的惊厥易感性可能取决于NMDA过程和NMDA受体的致敏或上调。我们的结果表明，DM对NMDA受体的抑制减轻了乙醇戒断症状。
