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Research Article

STUDIES ON THE TOXICITY AND BIOCHEMICAL MECHANISM OF ACTION OF 6-METHYL-2,3-QUINOXALINEDITHIOL CYCLIC CARBONATE (MORESTAN)

GARY P. CARLSON and KENNETH P. DUBOIS
Journal of Pharmacology and Experimental Therapeutics May 1970, 173 (1) 60-70;
GARY P. CARLSON
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KENNETH P. DUBOIS
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Abstract

A study was made of the acute and subacute toxicity of 6-methyl-2,3-quinoxalinedithiol cyclic carbonate (Morestan) and a possible metabolite, 6-methyl-2,3-quinoxalinedithiol. and their effects on various enzyme systems. The dithiol derivative was twice as toxic as Morestan to rats and mice. Male adult rats were twice as susceptible as females to both of the compounds. Weanling rats exhibited no sex difference in susceptibility and were more resistant than adults. Mice were less susceptible than rats and showed no sex difference. The toxicity to rats could not be altered by castration, administration of testosterone to females and estradiol to males. Pretreatment with phenobarbital decreased the toxicity to adult males and increased the toxicity to adult females. Morestan had a high cumulative toxicity when administered daily. Acutely toxic doses caused decreased activity, diarrhea, increased hematocrit values, decreased urination and a fall in blood pressure. Both compounds inhibited sulfhydryl enzymes including pyruvic dehydrogenase, succinic dehydrogenase, malate dehydrogenase and α-ketoglutarate oxidase. Reduced glutathione levels were lowered in the liver. Nitroreductase activity was reduced. Feeding Morestan in the diet for 90 days at 500 ppm resulted in decreased body weight, enlarged livers, inhibition of acetoacetate synthesis and inhibition of microsomal enzymes.

Footnotes

    • Received July 30, 1969.
    • Accepted January 27, 1970.
  • © 1970, by The Williams & Wilkins Company

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Journal of Pharmacology and Experimental Therapeutics
Vol. 173, Issue 1
1 May 1970
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Research Article

STUDIES ON THE TOXICITY AND BIOCHEMICAL MECHANISM OF ACTION OF 6-METHYL-2,3-QUINOXALINEDITHIOL CYCLIC CARBONATE (MORESTAN)

GARY P. CARLSON and KENNETH P. DUBOIS
Journal of Pharmacology and Experimental Therapeutics May 1, 1970, 173 (1) 60-70;

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Research Article

STUDIES ON THE TOXICITY AND BIOCHEMICAL MECHANISM OF ACTION OF 6-METHYL-2,3-QUINOXALINEDITHIOL CYCLIC CARBONATE (MORESTAN)

GARY P. CARLSON and KENNETH P. DUBOIS
Journal of Pharmacology and Experimental Therapeutics May 1, 1970, 173 (1) 60-70;
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