Tolerance does not develop to the suppressant effects of (−)-norpseudoephedrine on ingestive behavior in the rat

Abstract

(−)-Norpseudoephedrine (NPE), the enantiomer of cathine and a structural analog of phenylpropanolamine, shows anorectic and antidipsic effects that have been referred to its structural analogies with amphetamine. When amphetamine is chronically administered to rats, its anorectic effects fade out, water intake is progressively increased, and the diuretic response to the drug remains stable. Our previous studies show that chronic administration of NPE does not produce the typical amphetamine hyperdipsic response. In the present study, designed to obtain a more detailed picture of the ingestive and diuretic effects of chronic exposure to NPE, we evaluated the effects of 11 daily administrations of three doses of NPE (17, 32, and 56 mg/kg IP) on food and water intake, as well as on diuresis, in rats maintained in conditions of free access to food and water. Results show that all three doses inhibited food intake at 2 h, whereas only the highest dose inhibited food intake at 5 h. No differences between groups were detected at 24 h. These responses remained unchanged throughout the 11 days of treatment, and substitution of NPE with a solvent injection caused no rebound feeding. NPE treatment did not modify the ingestive response to a challenge injection of amphetamine, 0.56 and 1.0 mg/kg IP, given 1 day apart. Although NPE inhibited water intake throughout the experiment, it did so significantly only during the first 2 h postinjection. Urine output in the NPE-treated groups increased significantly on the first day only. These findings make it unlikely that the anorectic effects of NPE depend on an amphetamine-like mechanism of action. In addition, the short-lasting anorectic and antidipsic effects of NPE and the lack of tolerance to them raise the possibility of a therapeutic use of this drug as an adjuvant in the therapy of eating disorders characterized by binge episodes.