Kaur S, Starr M S
Department of Pharmacology, School of Pharmacy, London, UK.
Eur J Pharmacol. 1995 Jul 4;280(2):159-66. doi: 10.1016/0014-2999(95)00200-5.
Dextromethorphan has been reported to be a weak antagonist of the ion channel associated with the NMDA receptor, and to have putative antiparkinsonian activity in man. This study looked at the effects of dextromethorphan in normal and monoamine-depleted mice, to determine whether it exhibited a behavioural profile with regard to motor activity that was consistent with NMDA receptor blockade. In normal mice, 5-80 mg/kg i.p. dextromethorphan caused modest muscle relaxation at the highest dose in all animals; hyperlocomotion and stereotypy were evident at 40 mg/kg i.p. in a fraction of mice (4/14). In 24 h reserpine-treated mice, locomotion was reinstated by the dopamine D1 receptor agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF 38393, 30 mg/kg i.p.), the dopamine D2 receptor agonist N-n-propyl-N-phenylethyl-p-(3-hydroxyphenyl)ethylamine (RU 24213, 5 mg/kg s.c.) and L-3,4-dihydroxyphenylalanine (L-DOPA, 150 mg/kg i.p. in conjunction with benserazide 100 mg/kg i.p.). Dextromethorphan alone (10-40 mg/kg i.p.) caused non-significant arousal of monoamine-depleted mice, but potentiated synergistically movements elicited by SKF 38393 and L-DOPA, though not RU 24213. The possible use of dextromethorphan as an adjunct to L-DOPA in the treatment of Parkinson's disease in man, is discussed.
据报道，右美沙芬是与N-甲基-D-天冬氨酸（NMDA）受体相关的离子通道的弱拮抗剂，并且在人体中具有假定的抗帕金森病活性。本研究观察了右美沙芬对正常小鼠和单胺耗竭小鼠的影响，以确定其在运动活动方面是否表现出与NMDA受体阻断一致的行为特征。在正常小鼠中，腹腔注射5-80mg/kg的右美沙芬在所有动物的最高剂量下引起适度的肌肉松弛；腹腔注射40mg/kg时，部分小鼠（4/14）出现运动亢进和刻板行为。在利血平处理24小时的小鼠中，多巴胺D1受体激动剂盐酸2,3,4,5-四氢-7,8-二羟基-1-苯基-1H-3-苯并氮杂卓（SKF 38393，腹腔注射30mg/kg）、多巴胺D2受体激动剂N-正丙基-N-苯乙基-p-（3-羟基苯基）乙胺（RU 24213，皮下注射5mg/kg）和L-3,4-二羟基苯丙氨酸（左旋多巴，腹腔注射150mg/kg并联合苄丝肼腹腔注射100mg/kg）可恢复运动。单独使用右美沙芬（腹腔注射10-40mg/kg）引起单胺耗竭小鼠的唤醒作用不显著，但可协同增强SKF 38393和左旋多巴引发的运动，而对RU 24213则无此作用。文中讨论了右美沙芬作为左旋多巴辅助药物用于治疗人类帕金森病的可能性。
