Effects of the alpha 1a-adrenoceptor antagonist RS-17053 on phenylpropanolamine-induced anorexia in rats.

Activation of alpha 1-Adrenergic receptors via systemic administration of drugs such as phenylpropanolamine (PPA) and cirazoline results in the suppression of feeding in rats. Whether PPA acts via activation of the three currently identified alpha 1-Adrenoceptor subtypes is unknown. The intent of the present study was thus to examine the effects of systemic administration of the novel alpha 1a-Adrenoceptor antagonist RS-17053 on PPA-induced anorexia. Adult male rats (n = 6 to 8 per group) were pretreated (IP) with either 0, 0.1, 0.5, 2.5, or 10.0 mg/kg RS-17053 or with 2.0 mg/kg of the prototypical alpha 1-Adrenoceptor antagonist prazosin. Five minutes later, each rat was treated (IP) with either 0, 5, 10 or 15 mg/kg PPA. Food and water intakes were recorded for a 30 min period starting 10 min after the the treatment injection. Rats pretreated with vehicle and then treated with PPA exhibited a dose-dependent suppression of feeding with a maximal effect evident at the 15 mg/kg dose of PPA. Pretreatment with 2.0 mg/kg prazosin reversed the anorexic activity of PPA. Pretreatment with RS-17053 (0.1-2.5 mg/kg) did not alter either baseline feeding or the anorexic action of PPA. These results suggest that PPA does not act via the alpha 1a-Adrenergic receptor subtype to suppress food intake.