A BIOCHEMICAL AND TOXICOLOGICAL COMPARISON OF T.2636 AND MORPHINE

Abstract

After the repeated administration of T2636 to rats, the animals became tolerant to its toxic effects and to those of morphine. Similarly, morphine tolerant rats were found to be tolerant to T2636. The in vitro N-demethylation of both compounds by the liver microsomal enzymes was depressed in preparations from both T2636 and morphine tolerant rats. After withdrawal of T2636 from tolerant rats the pharmacological response of the animals to the drug and the liver microsomal N-demethylating activity returned to normal within 25 days. N-allyl normorphine, an antagonist of the pharmacological actions of both T2636 and morphine, inhibited the N-demethylation of both compounds. It is concluded that T2636 produces its biochemical and pharmacological effects by a similar mechanism to morphine.

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Document Details

Document Type
Technical Report
Publication Date
Dec 16, 1963
Accession Number
AD0355398

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  • L. Leadbeater

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