title: Genotype-treatment interaction between amantadine and chlorpromazine in the mouse.
abstract: 1. Repeated administration of amantadine prior to chlorpromazine to two different strains of mice altered both locomotor activity, concentrations of brain biogenic amines and selected major metabolites as a function of mouse strain. 2. Amantadine antagonized chlorpromazine effect on motility which was associated with increases in whole brain levels of homovanillic acid in the CDF-1 but not C57BL/6 mice. 3. Conversely, the treatment with amantadine prior to chlorpromazine reduced whole brain normetanephrine and 5-hydroxyindoleacetic acid levels from respective controls in the C57BL/6 and CDF-1 mice, respectively. 4. The results suggest that genetic factors underly differential alteration of brain dopamine and serotonin which may underly the mechanism of amantadine efficacy in neuroleptic-induced extrapyramidal disorders and to the variable responses to amantadine therapy.
authors.affiliation: Department of Pharmacology, University of North Dakota School of Medicine, Grand Forks 58203.
authors.forename: F S
authors.initials: FS
authors.lastname: Messiha
mesh_terms: D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D005838:Genotype; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains / Q000235:genetics / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D009647:Normetanephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
chemical_list: D001679:Biogenic Amines; D009647:Normetanephrine; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D000547:Amantadine; D002746:Chlorpromazine; D004298:Dopamine