The pharmacology of the anorexic effect of phenylpropanolamine

Phenylpropanolamine (PPA), the racemic mixture of d- and I-norephedrine, suppresses appetite in a variety of species and reduces body-fat content and weight. Explanations of the anorexic action of PPA have often started with the view that PPA is but a minimally potent variant of the amphetamine molecule. Yet studies conducted in the last 5 years reveal a number of important differences as to the site of action and neurochemical mechanism of action of amphetamine and PPA. The anorexic capacity of amphetamine is mediated by dopaminergic and beta-adrenergic activity within the perifornical hypothalamus (PFH). Direct injections of amphetamine within the PFH suppress feeding whereas PPA injections do not. Destruction of brain tissue that negates the anorexic action of amphetamine is without effect on PPA anorexia. Pharmacological blockade of dopamine receptors, using haloperidol, reduces amphetamine anorexia but is without effect on PPA anorexia. Yet, direct injections of PPA and amphetamine into the paraventricular hypothalamus suppress feeding. With regard to non-feeding behaviour, amphetamine markedly enhances locomotion and induces euphoria whereas PPA does not. These results strengthen the argument that PPA is not simply a variant of the amphetamine molecule but is an anorectic of its own class without the marked side-effects that compromise the anorexic capacity of amphetamine.