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Mouse strain‐dependent hepatic interaction of psychoactive agents with ethanol and biogenic aldehydes metabolizing enzymes
Author(s) -
Messiha F. S.
Publication year - 1991
Publication title -
human psychopharmacology: clinical and experimental
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.461
H-Index - 78
eISSN - 1099-1077
pISSN - 0885-6222
DOI - 10.1002/hup.470060111
Subject(s) - reserpine , chlorpromazine , amantadine , pharmacology , aldehyde dehydrogenase , enzyme , chemistry , ethanol , alcohol dehydrogenase , biochemistry , drug , potency , biology , in vitro
The effect of multiple dose regimens of amantadine, reserpine, chlorpromazine alone or combined on liver alcohol (L‐ADH) and aldehyde dehydrogenase (L‐ALDH) was studied in three strains of mice. A strain‐dependent difference between endogenous specific activity of these enzymes and their sensitivity to the agents studied was determined. The C 57 BL/6 mice showed most resistance to drug effect and possessed greater activity of mitochondrial L‐ALDH isoenzymes and L‐ADH than either ICR or BALB/C mouse strains, respectively. Amantadine induced both L‐ADH and mitochondrial L‐ALDH while reserpine inhibited them also as a function of mouse strain. Both reserpine‐and chlorpromazine‐mediated inhibition of albino ICR mouse L‐ADH and BALB/C mitochondrial L‐ALDH was alleviated by pretreatment with amantadine. This indicates antagonism between amantadine and these agents. The results suggest a genotypic sensitivity to drug action which may explain the individual sensitivity to the development of chlorpromazine and reserpine‐produced side‐effects, and the potency of amantadine in management of such drug‐induced adverse reactions.