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Xenobiotica
the fate of foreign compounds in biological systems
Volume 14, 1984 - Issue 11
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Original Article

Studies on N-demethylation of methamphetamine by liver microsomes of guinea-pigs and rats: The role of flavin-containing mono-oxygenase and cytochrome P-450 systems

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Pages 861-866 | Received 19 Jul 1983, Published online: 30 Sep 2009
 

Abstract

1. Relative participation of flavin-containing mono-oxygenase and cytochrome P-4S0 systems in N-hydroxylation of and formaldehyde release from methamphetamine were studied in vitro using liver microsomes of guinea-pigs and rats. In guinea pigs, only methimazole, an inhibitor of flavin-containing mono-oxygenase, significantly suppressed the above reactions.

2. Formaldehyde release from methamphetamine was significantly inhibited not only by methimazole but also by inhibitors of the cytochrome P-450 system in liver microsomes from rats, but not guinea-pigs.

3. Pretreatment of guinea-pigs with phenobarbital and 3-methylcholanthrene did not enhance the metabolism of methamphetamine.

4. Pretreatment of rats with phenobarbital but not 3-methylcholanthrene increased slightly the N-demethylation of methamphetamine by liver microsomes.

5. The results indicate that a marked species difference exists in the enzymes concerned with N-demethylation of methamphetamine. N-Oxidation predominates in guinea-pigs, whereas in rats, N-oxidation and C-oxidation of the methyl group participate equally as the initial reaction of the N-demethylation pathway.

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