Reis Janine, John Daniel, Heimeroth Antje, Mueller Hans-Helge, Oertel Wolfgang H, Arndt Torsten, Rosenow Felix
Department of Neurology, Interdisciplinary Epilepsy Center, Philipps-University, Marburg, Germany.
Neuropsychopharmacology. 2006 Dec;31(12):2758-66. doi: 10.1038/sj.npp.1301122. Epub 2006 Jun 14.
Amantadine-sulfate has been used for several decades to treat acute influenza A, Parkinson's disease (PD), and acute or chronic drug-induced dyskinesia. Several mechanisms of actions detected in vivo/in vitro including N-methyl-D-aspartate (NMDA)-receptor antagonism, blockage of potassium channels, dopamine receptor agonism, enhancement of noradrenergic release, and anticholinergic effects have been described. We used transcranial magnetic stimulation (TMS) to evaluate the effect of single doses of amantadine on human motor cortex excitability in normal subjects. Using a double-blind, placebo-controlled, crossover study design, motor thresholds, recruitment curves, cortical stimulation-induced silent period (CSP), short intracortical inhibition (ICI), intracortical facilitation (ICF), and late inhibition (L-ICI) in 14 healthy subjects were investigated after oral doses of 50 and 100 mg amantadine with single and paired pulse TMS paradigms. Spinal cord excitability was investigated by distal latencies and M-amplitudes of the abductor digiti minimi muscle. After intake of amantadine, a significant dose-dependent decrease of ICF was noticed as well as a significant increase of L-ICI as compared to placebo. The effect on ICF and L-ICI significantly correlated with amantadine serum levels. ICI was slightly increased after amantadine intake, but the effect failed to be significant. Furthermore, amantadine had no significant effects on motor thresholds, MEP recruitment curves, CSP, or peripheral excitability. In conclusion, a low dose of amantadine is sufficient in modulating human motor cortex excitability. The decrease of ICF and increase of L-ICI may reflect glutamatergic modulation or a polysynaptic interaction of glutamatergic and GABA-ergic circuits. Although amantadine has several mechanisms of action, the NMDA-receptor antagonism seems to be the most relevant effect on cortical excitability. As L-ICI can be influenced by this type of drug, it may be an interesting parameter for studies of motor learning and use-dependent plasticity.
硫酸金刚烷胺已被用于治疗甲型流感、帕金森病（PD）以及急慢性药物性运动障碍数十年。体内/体外检测到的几种作用机制包括N-甲基-D-天冬氨酸（NMDA）受体拮抗、钾通道阻滞、多巴胺受体激动、去甲肾上腺素能释放增强以及抗胆碱能作用。我们使用经颅磁刺激（TMS）来评估单剂量金刚烷胺对正常受试者人类运动皮层兴奋性的影响。采用双盲、安慰剂对照、交叉研究设计，在14名健康受试者口服50毫克和100毫克金刚烷胺后，使用单脉冲和双脉冲TMS范式研究运动阈值、募集曲线、皮层刺激诱发静息期（CSP）、短皮质内抑制（ICI）、皮质内易化（ICF）和晚期抑制（L-ICI）。通过小指展肌的远端潜伏期和M波幅研究脊髓兴奋性。服用金刚烷胺后，与安慰剂相比，ICF显著剂量依赖性降低，L-ICI显著增加。对ICF和L-ICI的影响与金刚烷胺血清水平显著相关。服用金刚烷胺后ICI略有增加，但效果不显著。此外，金刚烷胺对运动阈值、运动诱发电位募集曲线、CSP或外周兴奋性无显著影响。总之，低剂量的金刚烷胺足以调节人类运动皮层兴奋性。ICF的降低和L-ICI的增加可能反映了谷氨酸能调节或谷氨酸能与GABA能回路的多突触相互作用。尽管金刚烷胺有多种作用机制，但NMDA受体拮抗似乎是对皮层兴奋性最相关的作用。由于L-ICI可受此类药物影响，它可能是运动学习和使用依赖性可塑性研究的一个有趣参数。
