Biological disposition of rigid analogs of amphetamine

Tissue levels of amphetamine and of amphetamine analogs with a rigid conformation (2-aminoindan, 2-aminotetralin, and 2-aminobenzocycloheptene) were measured in rats by a spectrofluorometric method involving the reaction of the primary amine group with fluorescamine. All drugs were concentrated in tissues, the order of distribution being lungs greater than kidneys greater than liver=spleen=brain greater than muscle greater than fat=heart greater than blood. In brain, amphetamine and 2-aminoindan were present mostly in the supernatant fraction after high speed centrifugation onbrain homogenates; the two higher molecular weight drugs were present at slightly greater concentrations in the particulate fraction. All four drugs disappeared from rat brain with half-lives of 1-2 hr. Iprindole pretreatment increased drug levels in brain and prolonged the half-lives by two- to threefold. The data suggest that the biological disposition of the rigid analogs resembles generally that of amphetamine and that all of the drugs are probably metabolized by ring hydroxilation in the rat.