Effect of (−)- trans-PAT, a novel 5-HT 2C receptor agonist, on intake of palatable food in mice

Abstract

(1 R,3 S)-(−)- trans-1- phenyl-3-dimethyl amino-1,2,3,4- tetrahydronaphthalene (PAT) is a novel compound that has full-efficacy agonist activity at human 5-HT 2C receptors and inverse agonist/antagonist activity at 5HT 2A and 5HT 2B receptors. In the present paper we describe its effects on food intake in non-deprived C57BL/6 mice adapted to eating a palatable dessert meal each day. PAT showed a dose-related inhibition of food intake with a 50% inhibitory dose of 4.2 mg/kg. The dose–effect curve was similar to that obtained using WAY-161503. Abnormal behaviors were not observed by casual inspection following administration of PAT. The anorectic effect of PAT was additive with that of amphetamine. When PAT, or PAT + amphetamine, were injected 2 h before access to food, most of the anorectic activity had dissipated, indicating that PAT has a biologically effective period of about 1 h. Four daily injections of PAT were associated with some, but not complete loss of the initial anorectic effect; this differs from the rapid tolerance that has been reported to fenfluramine anorexia and suggests that different mechanism(s) are involved in the loss of anorexia.