Ziemann U, Chen R, Cohen L G, Hallett M
Human Cortical Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Neurology. 1998 Nov;51(5):1320-4. doi: 10.1212/wnl.51.5.1320.
To assess the acute effects of dextromethorphan (DM) on human motor cortical excitability.
DM, a noncompetitive N-methyl-D-aspartate receptor antagonist, has recently attracted clinical interest for its potential as a neuroprotective agent in various models of excitotoxicity. We were interested in learning whether this drug can modulate the excitability of the motor cortex in healthy subjects.
The effects of DM on the excitability of the normal human motor cortex were studied in eight healthy volunteers by means of focal transcranial magnetic stimulation before and 1.5, 4, 6.5, and 24 hours after a single oral dose of 150 mg DM. Motor evoked potentials (MEPs) were recorded from the relaxed abductor digiti minimi muscle. Measures of motor cortical excitability were motor threshold, MEP recruitment, duration of the cortical silent period, and intracortical inhibition and facilitation. In addition, the authors explored spinal and neuromuscular excitability by means of F waves, duration of the peripheral silent period, and maximum M wave.
Intracortical inhibition increased temporarily, intracortical facilitation decreased, and the cortical silent period lengthened slightly. Motor threshold, MEP recruitment, and spinal and peripheral motor excitability were not affected significantly.
Our findings suggest that DM can exert a significant suppression of the excitatory drive in the normal human cortex, which may be relevant for its potential therapeutic use in excitotoxicity-related neurologic disease. Furthermore, the noninvasive technique described may prove useful in preclinical studies to assess the effects on motor cortical excitability induced by new modulators of glutamatergic transmission currently under development.
评估右美沙芬（DM）对人类运动皮质兴奋性的急性影响。
DM是一种非竞争性N-甲基-D-天冬氨酸受体拮抗剂，最近因其在各种兴奋性毒性模型中作为神经保护剂的潜力而引起临床关注。我们想了解这种药物是否能调节健康受试者运动皮质的兴奋性。
在8名健康志愿者中，通过单次口服150mg DM前以及服药后1.5、4、6.5和24小时进行局灶性经颅磁刺激，研究DM对正常人类运动皮质兴奋性的影响。从放松的小指展肌记录运动诱发电位（MEP）。运动皮质兴奋性的测量指标包括运动阈值、MEP募集、皮质静息期持续时间以及皮质内抑制和易化。此外，作者通过F波、外周静息期持续时间和最大M波来探究脊髓和神经肌肉兴奋性。
皮质内抑制暂时增加，皮质内易化减少，皮质静息期略有延长。运动阈值、MEP募集以及脊髓和外周运动兴奋性未受到显著影响。
我们的研究结果表明，DM可对正常人类皮质的兴奋性驱动产生显著抑制作用，这可能与其在兴奋性毒性相关神经疾病中的潜在治疗用途有关。此外，所描述的非侵入性技术可能在临床前研究中证明有用，以评估目前正在开发的新型谷氨酸能传递调节剂对运动皮质兴奋性的影响。
