Behavioral and neurochemical evaluation of phenylpropanolamine

(+/-)-Phenylpropanolamine (PPA), a widely available anorectic and decongestant, was evaluated in several behavioral paradigms in rhesus monkeys and for central nervous system neurotoxicity in rats. PPA (1-30 mg/kg intragastric) reduced food intake in rhesus monkeys but was not self-administered i.v. (0.3-10 mg/kg/injection) by monkeys experienced in drug self-administration. PPA (30-100 mg/kg intragastric) resulted in amphetamine-like responding in two of four monkeys trained in a drug discrimination paradigm to discriminate d-amphetamine from saline. In rats, a 4-day injection regimen of high doses of PPA (200 and 400 mg/kg/day) resulted in approximately a 20% depletion of dopamine in the frontal cortex but failed to deplete dopamine, norepinephrine or serotonin in any other brain region studied. Thus, PPA is an effective anorectic in rhesus monkeys that, based upon drug discrimination results, would be expected to have limited amphetamine-like subjective effects and only at doses well in excess of effective anorectic doses. However, based upon self-administration results, PPA would not be predicted to have amphetamine-like dependence potential. Moreover, repeated administration of PPA did not produce the severe central nervous system neurotoxicity associated with many other amphetamine congeners.