Benzphetamine metabolism, effect

It is clear from these comments that the biochemical and toxicological effects seen after various inducers may be markedly different. This is illustrated by the effects of different inducers on the metabolism of various substrates examined in vitro and shown in Table 5.22. It can be seen that in some cases the inducers cause no change in the metabolism, whereas in other cases, metabolism is increased or even decreased. Thus studies in vitro showed that pretreatment with phenobarbital markedly increased benzphetamine metabolism but had no effect on benzo(a)pyrene metabolism. Conversely, 3-methylcholanthrene pretreatment increased benzo (a) pyrene metabolism but markedly decreased benzphetamine metabolism. 

Benzphetamine is a methamphetamine whose tertiary amine also carries a benzyl group. The likelihood of metabolic N-debenzylation yielding methamphetamine would, of course, explain its effects. Diethylpropion (No. 14) is an interesting compound because of its particularly involved metabolic degradation, which is initiated by stepwise N-deethylation and keto reduction to a P-OH. These active metabolites, presumably with the parent compound, explain both anorexiant and CNS effects, as well as the reduced level of the latter when compared with amphetamine. Subsequent oxidations all the way to benzoic, hydrox-ybenzoic, and mandelic acids all lead to inactivation. 

---