Abstract
The inhibition of microsomal mixed-function oxidations (MFO) by amphetamines was greatest for those compounds capable of forming metabolic intermediate (MI) complexes with cytochrome P-450 at fast rates. Ethylmorphine N-demethylase was least sensitive, p-nitroanisole O-demethylase was intermediate, and benzopyrene hydroxylase was the most sensitive reaction to amphetamine inhibition. Formation of MI complexes prior to initiating MFO reactions increased the degree of inhibition by adding a noncompetitive component to the initial competitive inhibition. This increased inhibition was only evident in microsomes from phenobarbital-pretreated animals, not those from untreated or 3-methylcholanthrene-pretreated animals. Hepatic MFO reactions in rabbit were more susceptible to inhibition than those of rat. In rabbit, lung benzopyrene hydroxylase was more susceptible to inhibition than liver. The formation of MI complexes from amphetamines can be a significant contributing factor to the inhibition of mixed-function oxidase reactions.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
