The effects of stereoisomers of 2- and 9- aminobenzonorbornenes on food intake, brain serotonin concentration and monoamine oxidase activity in the rat.

To evaluate the importance of the conformation of amphetamine in eliciting its various central nervous system effects, the conformationally defined analogs of amphetamine. In this series of isomeric amines, the exo-2 and anti-9 isomers resemble the fully extended conformation of amphetamine, whereas the endo-2 and syn-9 isomers resemble the folded conformation. The exo-2 and anti-9 isomers were equally as effective in reducing food intake in the rat, but were much less potent than amphetamine. The endo-2 and syn-9 isomers had no effect on food intake up to a dose of 40 mg/kg. These latter two isomers also caused very little inhibition of monoamine oxidase in vitro. The exo-2 and anti-9 isomers, however, were nearly as effective as amphetamine in inhibiting monoamine oxidase type A, but only amphetamine and the anti-9 isomer inhibited monoamine oxidase type B. The effects at anorectic doses on brain serotonin (5-HT) concentration were also studied. Although amphetamine had no effect on the 5-HT concentration and fenfluramine decreased its concentration, the exo-2 and anti-9 isomers caused a significant increase in brain 5-HT. The anti-9 isomer caused a 14% increase in 5-HT, whereas the exo-2 isomer gave a 49% increase over controls. The data suggest that the fully extended conformation of amphetamine is preferred over the folded conformation for eliciting its biological responses, although the rigid analogs were less potent than amphetamine.