Stimulatory effect of 6-aminochrysene and congeners on zoxazolamine metabolism

M. G. Donelli, S. Garattini

Research output: Contribution to journalArticlepeer-review

Abstract

6-Aminochrysene (6AC) and a series of derivatives, which are selective inhibitors of the growth of a spontaneous mammary carcinoma in mice and a rhabdomyosarcoma in rats, antagonize the muscular paralysis induced by zoxazolamine in Sprague-Dawley male rats. This effect is shown to be maximal 24 hr after treatment and decreases at longer intervals. The route of administration of both drugs does not appear to be important. Measurements of blood and brain zoxazolamine in rats pretreated with 6AC indicate lower levels of the compound as compared with controls. Furthermore in vitro experiments show that the 9000g liver fraction of 6AC pretreated rats metabolize zoxazolamine twice as rapidly as controls. On the contrary, 6AC pretreatment does not reduce the duration of paralysis induced by carisoprodol, the sleeping time by pentobarbital, the convulsions or the toxicity by strychnine. Moreover, the in vitro metabolism of two microsomal substrates, p-NO2 anisol and aniline, is not affected by 6AC. These findings may well account for the strong specific inhibition of 6AC on zoxazolamine induced paralysis and are consistent with the hypothesis that 6AC resembles polycyclic hydrocarbons in its stimulating activity on hepatic microsomal enzymes.

Original languageEnglish
Pages (from-to)2049-2055
Number of pages7
JournalBiochemical Pharmacology
Volume20
Issue number8
DOIs
Publication statusPublished - 1971

ASJC Scopus subject areas

  • Pharmacology

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