Genotype-treatment interaction between amantadine and chlorpromazine in the mouse.
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.
Messiha
F S
FS
Department of Pharmacology, University of North Dakota School of Medicine, Grand Forks 58203.
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
D001679:Biogenic Amines; D009647:Normetanephrine; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D000547:Amantadine; D002746:Chlorpromazine; D004298:Dopamine