Biochemical pharmacology of some chlorinated 3-phenyl-piperidines in rats

Chlorinated 3-phenyl-piperidines were administered to rats with the expectation--based on structural similarities--that they might resemble chlorinated amphetamines pharmacologically. The 3-chloro, 4-chloro, and 3,4-dichloro compounds all lowered serotonin and 5-hydroxyindoleacetic acid levels in rat brain, whereas the 2-chloro compound had no effect. The brain levels and half-lives of the four compounds suggested that the compounds might be metabolized by hydroxylation at the 4- position of the phenyl ring. Desmethylimipramine, an inhibitor of amphetamine hydroxylation in the 4- position, markedly elevated brain levels of the 2-chloro compound and to a lesser extent of the 3-chloro compound. The 2-chloro compound did not lower brain serotonin levels even in desmethylimipramine-treated rats, however. The results suggest that some pharmacologic properties of the chlorinated 3-phenyl-piperidines are indeed similar to those of chlorinated amphetamines.