Enhancement of phenylpropanolamine anorexia by proglumide in rats

Although a number of studies have characterized the anorectic state induced by phenylpropanolamine (PPA), the mechanism by which this drug suppresses appetite remains elusive. PPA inhibits gastric emptying at doses that also suppress appetite as does the gut hormone cholecystokinin (CCK). To evaluate whether PPA anorexia results via an action on gut CCK activity, rats in the present study were treated (IP) with either 0.9% saline or 150 mg/kg proglumide, a CCK receptor antagonist, 30 minutes before a 15 min feeding trial and then injected (IP) 5 min prior to the trial with either 0.9% saline, 5 mg/kg PPA, 10 mg/kg PPA, 8 ug/kg CCK or 16 ug/kg CCK. Although 150 mg/kg proglumide antagonized CCK anorexia, this dose of proglumide significantly enhanced the anorectic action of PPA. These results suggest that PPA does not act via an endogenous CCK system to suppress feeding.