Bisaga Adam, Evans Suzette M
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA.
Psychopharmacology (Berl). 2004 Feb;172(1):16-24. doi: 10.1007/s00213-003-1617-5. Epub 2003 Oct 3.
Alcohol effects in humans involve N-methyl- d-aspartate (NMDA) receptor-mediated glutamatergic neurotransmission. It has been proposed that NMDA receptor antagonists may be effective in the treatment of alcohol dependence.
This study evaluated the acute effects of memantine, an NMDA receptor antagonist, on the subjective, physiological, and performance effects of alcohol in moderate (10-30 drinks per week) alcohol drinkers.
Eighteen volunteers without alcohol dependence were tested using a double-blind design with three 3-day long inpatient phases separated by at least a 2-week wash-out period. Memantine (0, 15, and 30 mg) was administered 4 h before alcohol (1.5 g/l body water), which was given in four divided doses every 20 min.
Pretreatment with memantine attenuated the craving for alcohol before alcohol administration, but not after alcohol was given. Memantine increased the dissociative effects of alcohol, without altering its sedative, stimulant, and overall intoxicating effects. Memantine also did not affect alcohol-induced impairment in performance, physiological changes, or pharmacokinetics. Memantine increased subjective reports of dissociation, confusion, and stimulation, and impaired motor coordination on the balance task.
Memantine was well tolerated in combination with alcohol. The findings suggest that NMDA receptor neurotransmission may be involved in alcohol craving and alcohol-induced subjective dissociative effects.
酒精对人类的影响涉及N-甲基-D-天冬氨酸（NMDA）受体介导的谷氨酸能神经传递。有人提出，NMDA受体拮抗剂可能对酒精依赖的治疗有效。
本研究评估了NMDA受体拮抗剂美金刚对中度饮酒者（每周饮酒10 - 30次）饮酒后的主观、生理和行为影响的急性效应。
18名无酒精依赖的志愿者采用双盲设计进行测试，分为三个为期3天的住院阶段，各阶段之间至少间隔2周的洗脱期。在饮酒（每千克体重1.5克酒精）前4小时给予美金刚（0、15和30毫克），酒精分四次给药，每次间隔20分钟。
美金刚预处理可减轻饮酒前对酒精的渴望，但饮酒后则无此效果。美金刚增强了酒精的分离效应，但未改变其镇静、兴奋和整体中毒效应。美金刚也未影响酒精所致的行为损害、生理变化或药代动力学。美金刚增加了分离、困惑和兴奋的主观报告，并损害了平衡任务中的运动协调性。
美金刚与酒精联合使用耐受性良好。研究结果表明，NMDA受体神经传递可能与酒精渴望及酒精所致的主观分离效应有关。
