title: Amantadin e tremor, a 5-hydroxytryptamine-mediated response?
abstract: Amantadine-induced tremor has been investigated using mice. Experiments with, mebanazine, reserpine, diethyldithiocarbamate, and p-chlorophenylalanine suggest that the tremorgenic action of amantadine is influenced by a balance between three putative central nervous system (CNS) transmitters: noradrenaline, dopamine and 5-hydroxytryptamine (5-HT). Drugs which reduce the concentration of the catecholamines in brain increase amantadine induced tremor. p-Chlorophenylalanine, which specifically depletes brain 5-HT, antagonises amantadine-induced tremor. An ED50 (tremor) dose of amantadine decreases the concentration of 5-hydroxy-indoleacetic acid (5-HIAA) in rat brain, particularly when this elevated due to pretreatment with 5-hydroxytryptophan. Neither inhibition of monoamine oxidase nor reduction of 5-HT-reuptake appear to be responsible for this decrease. Experiments on rat fundus suggest that amantadine increased the sensitivity of receptors to 5-HT. A similar mechanism of action in the CNS could explain both the tremor and the decrease in brain 5-HIAA. The possible relevance of these findings is discussed with respect to the known anti-Parkinson action of amantadine.
mesh_terms: D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects; D010134:Fenclonine / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008995:Monoamine Oxidase / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology*; D013270:Stomach / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology; D014202:Tremor / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D013859:Thiocarbamates; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D012110:Reserpine; D000547:Amantadine; D008995:Monoamine Oxidase; D010134:Fenclonine