Comparative effects of two dithiocarbamates disulfiram and thiram, on adrenal catecholamine content and on plasma dopamine-beta-hydroxylase activity.
Both disulfiram (tetraethylthiuram disulfide), an alcohol aversive drug, and thiram (tetramethyl-thiuram disulfide), a widely used pesticide, significantly increased the dopamine pool in the adrenal glands of dosed rats. The dopamine increase was detectable within 4 h of oral dosing with 100 mg/kg of either dithiocarbamate and peaked 24 h later at 10 times control values. In control rats the dopamine turnover was 0.51 h-1 as calculated by the assumed first order decline of dopamine after a single injection of alpha-methyl-p-tyrosine (alpha-MT, 400 mg/kg i.p.) resulting in a dopamine-beta-hydroxylase (DBH) activity of 0.73 nmol/h per pair of adrenals. In the adrenals of rats pretreated with thiram and then injected with alpha-MT, the adrenal dopamine content did not significantly decline, indicating that thiram reduced the conversion of dopamine to noradrenaline, eventually leading to the observed dopamine increase. Plasma DBH activity was significantly reduced 4 h and 24 h after dosing with thiram, but was unchanged after treatment with disulfiram. The determination of plasma DBH activity could be a marker to monitor the effect of thiram on catecholamine metabolism in occupationally exposed workers but not that of disulfiram in abstinent alcoholics.
Caroldi
S
S
Università degli Studi di Padova, Istituto di Medicina del Lavoro, Italy.
De Paris
P
P
D000284:Administration, Oral; D000311:Adrenal Glands / Q000737:chemistry* / Q000187:drug effects; D000427:Alcohol Deterrents / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002395:Catecholamines / Q000032:analysis*; D004221:Disulfiram / Q000008:administration & dosage / Q000633:toxicity*; D004299:Dopamine beta-Hydroxylase / Q000097:blood*; D005659:Fungicides, Industrial / Q000008:administration & dosage / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D008297:Male; D008781:Methyltyrosines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013893:Thiram / Q000008:administration & dosage / Q000633:toxicity*
D000427:Alcohol Deterrents; D002395:Catecholamines; D005659:Fungicides, Industrial; D008781:Methyltyrosines; D013893:Thiram; D004299:Dopamine beta-Hydroxylase; D004221:Disulfiram