Effect of tremorogenic and antitumor agents on enzymes regulating a minor metabolic pathway of biogenic amines: an hypothesis for the underlying mechanism.
The effects of some tremor-producing and antitremor agents on the enzymes sequentially metabolizing ethanol and acetaldehyde in addition to biogenic-amine-derived aldehyde intermediates were studied in mouse liver preparations. Aldehyde but not alcohol dehydrogenase was differentially stimulated by the compounds studied in vitro. This effect was confined to the mitochondrial enzyme and was isoenzyme-dependent. The results indicate difference between in vitro and in vivo effects and suggest a role for mitochondrial aldehyde dehydrogenase in metabolic detoxification of endogenous biogenic aldehydes in the presence of alcohol which may explain the worsening of drug-induced tremor by ethanol.
Messiha
F S
FS
Texas Tech University Health Sciences Center, School of Medicine, Lubbock.
D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001679:Biogenic Amines / Q000378:metabolism*; D010134:Fenclonine / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014202:Tremor / Q000139:chemically induced
D000970:Antineoplastic Agents; D001679:Biogenic Amines; D009292:Narcotic Antagonists; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D010134:Fenclonine