Implantation of disulfiram in rats.
The biochemical and pharmacological effects of disulfiram implantation were studied in rats. Sterile disulfiram pellets (1000 mg/kg) were implanted subcutaneously. Groups of 5 rats were killed after 3, 7, 14, 28 and 56 days. The release of disulfiram during the first week corresponded to a daily dose of 12--16 mg/kg and during the following period to 5--8 mg/kg. The activity of the low-Km aldehyde dehydrogenase in liver and brain, the carboxylesterase activity in liver and the dopamine-beta-hydroxylase activity in heart were significantly decreased by approximately 45, 35, 20 and 35% respectively at all periods tested. The rate of ethanol elimination, the activity of monoamine oxidase in the brain, and the content of cytochrome P-450 in the liver were unaffected. The level of norepinephrine in the brain was slightly decreased after 14 days. The acetaldehyde level in blood after ethanol injection (1.0 g/kg) was 55--60 microM in the disulfiram group and 25--30 microM in the control group. Ethanol administration caused a slightly decreased blood pressure and increased respiratory rate 14 days after implantation but not after 28 days.
D000079:Acetaldehyde / Q000097:blood; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D002395:Catecholamines / Q000378:metabolism; D004221:Disulfiram / Q000008:administration & dosage* / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004343:Drug Implants; D000431:Ethanol / Q000097:blood; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D051381:Rats; D012119:Respiration / Q000187:drug effects
D002395:Catecholamines; D004343:Drug Implants; D000431:Ethanol; D007770:L-Lactate Dehydrogenase; D004299:Dopamine beta-Hydroxylase; D000445:Aldehyde Oxidoreductases; D000079:Acetaldehyde; D004221:Disulfiram