Reversal of cirazoline- and phenylpropanolamine-induced anorexia by the alpha 1-receptor antagonist prazosin.

Phenylpropanolamine (PPA) is a phenethylamine anorectic drug that exerts direct agonist effects predominantly on alpha 1-adrenoceptors, with some alpha 2-adrenergic activity. Microinjections of PPA, as well as the alpha 1-adrenergic receptor agonists cirazoline, methoxamine, and 1-phenylephrine, into rat paraventricular nucleus (PVN) suppress feeding. The present study further evaluates the alpha 1-adrenergic basis of PPA-induced anorexia by examining the effects of systemic injections of the alpha 1-adrenergic antagonist prazosin (PRAZ, 2 and 5 mg/kg, IP) on the anorexia induced by systemic injections of PPA (5, 10, and 20 mg/kg, IP), as well as cirazoline (0.05, 0.1, and 0.2 mg/kg, IP). Although neither PRAZ dose alone altered food intake in the present study, 2 mg/kg PRAZ effectively reversed the feeding-suppressive effects of both PPA and cirazoline. These results strongly support the hypothesis that alpha 1-adrenoceptor stimulation mediates the anorexia induced by drugs such as PPA and cirazoline.