Modification of mouse liver alcohol and aldehyde-dehydrogenase by chlorpromazine

The in vivo and in vitro effect of chlorpromazine (CPZ) on female mouse liver alcohol dehydrogenase (L-ADH) and mitochondrial aldehyde dehydrogenase (L-ALDH) was studied as a function of illumination conditions. Chlorpromazine was injected once daily in a gradual dose build-up from 5 to 30 mg/kg, i.p., over 21 consecutive days. This resulted in a noncompetitive inhibition of endogenous L-ALDH of mice housed under UV light exposure but not those maintained under standard laboratory fluorescent lighting and receiving identical CPZ treatment. No changes occurred in L-ADH in vivo but a noncompetitive inhibition of mouse L-ADH was determined in the presence of 50 muMol of CPZ in vitro. The results are discussed in reference to possible toxic mechanism underlying CPZ and ethanol interaction.