EFFECTS ON FOOD AND WATER-INTAKE OF THE ALPHA-1-ADRENOCEPTOR AGONISTS AMIDEPHRINE AND SK-AND-F-89748

Activation of alpha-1 adrenoceptors, via systemic injection of agonists such as cirazoline and phenylpropanolamine (PPA), reliably suppresses food intake in rats. These effects are thought to result from stimulation of central alpha1-adrenoceptors within the rat paraventricular hypothalamic nucleus (PVN), based on studies in which direct injections of cirazoline, methoxamine, phenylephrine and PPA into PVN suppress food intake. Because relatively few alpha-1-agonists have been tested to date using the systemic route of exposure, the present study examined the effects of the alpha1-adrenoceptor agonists amidephrine and SKF-89748 on food and water intake. Adult male rats received systemic injections (IP) of either amidephrine (0.025, 0.05, 0.01 mg/kg) or of SK&F 89748 (0.01, 0.02, and 0.04 mg/kg). Amidephrine markedly suppressed food intake (ED50=0.49 mg/kg) and water intake (ED50=0.50 mg/kg), while SK&F 89748 marginally suppressed food intake (ED50=0.37 mg/kg) and was less potent in suppressing water intake (ED50=0.76 mg/kg). These results document that systemic injection of the alpha1-adrenoceptor agonists amidephrine and SK&F 89748 induces anorexia with amidephrine exerting greater potency than SK&F 89748. These results further support the hypothesis that stimulation of alpha1-adrenoceptors suppresses food intake.