Research article summary (published 12 Jun 2006):

Modulation of human motor cortex excitability by single doses of amantadine.

Full Abstract

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.

Author information

Author/s: Reis, Janine (J); John, Daniel (D); Heimeroth, Antje (A); Mueller, Hans-Helge (HH); Oertel, Wolfgang H (WH); Arndt, Torsten (T); Rosenow, Felix (F);

Affiliation: Department of Neurology, Interdisciplinary Epilepsy Center, Philipps-University, Marburg, Germany.

Journal and publication information

Publication Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology), published in United States. (Language: eng)

Reference: 2006-Dec; vol 31 (issue 12) : pp 2758-66

Dates: Created 2006/11/19; Completed 2007/01/05;

PMID: 16794570, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult Amantadine - administration & dosage Antiparkinson Agents - administration & dosage Cross-Over Studies Dose-Response Relationship, Drug Double-Blind Method Drug Administration Schedule Efferent Pathways - drug effects; physiology Electromyography Evoked Potentials, Motor - drug effects; physiology Excitatory Amino Acid Antagonists - administration & dosage Female

Female Glutamic Acid - metabolism Humans Male Motor Cortex - drug effects; physiology Muscle, Skeletal - innervation; physiology Neural Inhibition - drug effects; physiology Neural Pathways - drug effects; physiology Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; metabolism Synaptic Transmission - drug effects; physiology Transcranial Magnetic Stimulation gamma-Aminobutyric Acid - metabolism

Associated Chemicals: Antiparkinson Agents (0) ; Excitatory Amino Acid Antagonists (0) ; Receptors, N-Methyl-D-Aspartate (0) ; gamma-Aminobutyric Acid (56-12-2) ; Glutamic Acid (56-86-0) ; Amantadine (768-94-5)

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