Abstract
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.
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