Disulfiram-like effect of diethyl maleate on barbiturate-induced hypnosis and 5-hydroxytryptamine metabolism.
Diethyl maleate (DEM, 600 mg kg-1 i.p.) significantly potentiated hexobarbitone hypnosis and lowered plasma hexobarbitone level on awakening. Sleeping time following intracerebroventricular (i.c.v.) injection of phenobarbitone was also prolonged by DEM treatment. When administered to DEM-treated rats, L-tryptophan (50 mg kg-1 i.p.) significantly potentiated hexobarbitone hypnosis, although alone it had no effect in control rats. DEM markedly diminished the activity of brain low-Km aldehyde dehydrogenase (A1DH) and the formation of 5-hydroxyindoleacetic acid from 5-hydroxytryptamine (5-HT) without affecting MAO activity in various areas of the brain. Conversely, the protein-bound radioactivity derived from i.c.v. [14C]-5-HT was increased by DEM treatment. These results showed that DEM is comparable with disulfiram, a brain A1DH inhibitor, in terms of its effect on 5-HT metabolism and barbiturate hypnosis.
D000444:Aldehyde Dehydrogenase; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D004221:Disulfiram / Q000494:pharmacology*; D004347:Drug Interactions; D007276:Injections, Intraventricular; D008297:Male; D008298:Maleates / Q000494:pharmacology*; D008995:Monoamine Oxidase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects*
D001463:Barbiturates; D008298:Maleates; D012701:Serotonin; D000445:Aldehyde Oxidoreductases; D000444:Aldehyde Dehydrogenase; D008995:Monoamine Oxidase; C014476:diethyl maleate; D004221:Disulfiram