Differential modulation of mouse brain biogenic amines by haloperidol and pimozide: implications in Tourette's syndrome.
1. A comparison between the effect of equal dose regimens of Tourette's medications on mouse motor activity and regional brain monoamines suggests differential responses which may underlie drug-induced side-effects. 2. Haloperidol was more potent than pimozide in altering striatal dopamine concentration which may account for the greater incidence of haloperidol-induced extrapyramidal disorders compared to pimozide. 3. Pimozide, but not the haloperidol treatment, altered brain serotonin concentrations to suggest a decrease in turnover rate which may underlie pimozide-caused sedation in Tourette's syndrome. 4. Pimozide was more potent than haloperidol in duration of behavioral depression which suggests differential dopamine receptor subtypes blockade. 5. Pimozide was more potent than haloperidol in altering 3 of the 6 brain regions content of norepinephrine-derived normetanephrine which may be responsible for the increase in blood pressure reported during pimozide treatment.
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Department of Pharmacology, University of North Dakota School of Medicine, Grand Forks 58203.
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004195:Disease Models, Animal; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D009647:Normetanephrine / Q000494:pharmacology; D009928:Organ Specificity; D010868:Pimozide / Q000494:pharmacology*; D012016:Reference Values; D005879:Tourette Syndrome / Q000503:physiopathology*
D001679:Biogenic Amines; D009647:Normetanephrine; D010868:Pimozide; D006220:Haloperidol