Tourette's medications: effect on minor oxidative and reductive pathways of biogenic amines.
The effect of acute treatment of two major Tourette's drugs, haloperidol and pimozide given 60 mg/kg, IP over 48 hr, on hepatic alcohol dehydrogenase (L-ADH) and aldehyde dehydrogenase was studied in the female mouse. The effect of these drugs on heart cytoplasmic lactate dehydrogenase (H-LDH) isoenzyme LDH1 (M) and LDH2 (H) was also measured. Both haloperidol and pimozide significantly inhibited cytoplasmic L-ADH and L-ALDH from controls. Conversely, the haloperidol treatment was associated with induction of both H-LDH isoenzymes studied. Injection of pimozide, 25 mg/kg, IP, to rats with preference to ethanol drinking, caused aversion to voluntary intake of 5% ethanol consumption. This suggests that pimozide produced inhibition of L-ADH in another species and thereby causing aversion to ethanol drinking or may be related to dopaminergic antagonist property. This inhibition of these drugs on the oxidative and reductive pathways of biogenic amine aldehydes may be implicated in and/or associated with the underlying mechanism(s) of action.
Messiha
F S
FS
Texas Tech University Health Sciences Center, School of Medicine, Lubbock.
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000428:Alcohol Drinking / Q000187:drug effects; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D010868:Pimozide / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D005879:Tourette Syndrome / Q000188:drug therapy* / Q000378:metabolism
D001679:Biogenic Amines; D010868:Pimozide; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D006220:Haloperidol