LACK OF INVOLVEMENT OF 4-HYDROXYNOREPHEDRINE IN PHENYLPROPANOLAMINE-INDUCED ANOREXIA IN RATS

The anorexic effects of phenylpropanolamine (PPA) appear to be qualita tively different in humans and rats. One factor that may account for t hese differences is that PPA is excreted essentially unchanged in huma ns, while nearly 30% is metabolized into 4-hydroxynorephedrine (4-OHN) in rats. To investigate the contribution of 4-OHN to the anorexic pro perties of PPA, this experiment compared the effects of equal doses (0 .0-20.0 mg/kg, IP) of both drugs on eating and drinking during restric ted feeding trials in the same group of food-deprived, female rats. Bo th 15.0 and 20.0 mg/kg of PPA significantly decreased eating when comp ared to saline vehicle, while 5.0-20.0 mg/kg of the drug reduced prand ial drinking. In comparison, only the highest dose of 4-OHN (20.0 mg/k g) significantly suppressed food and water intake. When the percentage of reduction produced by corresponding doses of the two drugs was com pared, PPA proved to be more than twice as potent as 4-OHN. It is conc luded that, at the doses used, 4-OHN is unlikely to significantly cont ribute to reductions in deprivation-induced eating produced by the acu te administration of PPA.