Reversal of phenylpropanolamine anorexia in rats by the alpha-1 receptor antagonist benoxathian.

Phenylpropanolamine (PPA) is a phenethylamine anorectic drug that exerts direct agonist effects predominantly on alpha-1 adrenergic receptors, with some alpha-2 adrenergic activity. Direct injections of PPA as well as the alpha-1 agonist 1-phenylephrine into rat paraventricular nucleus (PVN) suppress feeding. In the present study, we evaluate the hypothesis that systemic PPA acts within the PVN on an alpha-1 receptor population to suppress feeding. Accordingly, adult male rats were prepared with a unilateral guide cannula aimed at the PVN. Microinjection of the alpha-1 adrenergic receptor antagonist benoxathian (0, 2.5, 5.0 or 10.0 nmol) into the PVN was found to have no effect on baseline feeding behavior. Microinjection of 10.0 nmol benoxathian into the PVN completely reversed the anorexia induced by 2.5, 5.0 or 10.0 mg/kg PPA (IP), yet did not alter the hypodipsia produced by PPA. These data strongly suggest that PPA anorexia is mediated by an alpha-1 adrenergic satiety mechanism within the PVN.