Abstract
The cytochrome P-450-dependent microsomal metabolism of amphetamine and N-substituted amphetamines can result in the formation of a complex which absorbs maximally at 455 nm. In normal rat liver microsomes, this complex formation is either very slow or nonexistent, depending upon the amphetamine substrate used. Phenobarbital pretreatment of rats, which increases cytochrome P-450 concentration up to 3-fold and NADPH-cytochrome c reductase activity up to 2-fold, dramatically enhances the rate of formation of the complex for all substrates examined, up to 30-fold for norbenzphetamine and 10-fold for d-amphetamine. Pretreatment of rats with 3-methylcholanthrene, although producing a 2-fold increase in total cytochrome P-450 species, decreases the rate of complex formation below that observed in normal animals. Linear regression analysis of the results from phenobarbital-pretreated rats suggests that 455-nm complex formation from amphetamines is a uniquely sensitive indication of induction by this class of inducer.
Footnotes
- Received December 21, 1973.
- Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics
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