Effect of (-)-trans-PAT, a novel 5-HT2C receptor agonist, on intake of palatable food in mice.
(1R,3S)-(-)-trans-1-phenyl-3-dimethylamino-1,2,3,4-tetrahydronaphthalene (PAT) is a novel compound that has full-efficacy agonist activity at human 5-HT2C receptors and inverse agonist/antagonist activity at 5HT2A and 5HT2B 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.
Rowland
Neil E
NE
Department of Psychology, University of Florida, Gainesville, USA. nrowland@ufl.edu
Crump
Erica M
EM
Nguyen
Nancy
N
Robertson
Kimberly
K
Sun
Zhuming
Z
Booth
Raymond G
RG
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001067:Appetite Depressants; D002395:Catecholamines / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004361:Drug Tolerance; D004435:Eating / Q000187:drug effects*; D005260:Female; D005518:Food Preferences / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011719:Pyrazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
C502777:8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino(1,2-a)quinoxalin-5(6H)-one; D001067:Appetite Depressants; D002395:Catecholamines; D011719:Pyrazines; D011810:Quinoxalines; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists; D013764:Tetrahydronaphthalenes; C084981:1-phenyl-3-dimethylamino-1,2,3,4-tetrahydronaphthalene; D000661:Amphetamine