Effect of (-)-trans-PAT, a novel 5-HT2C receptor agonist, on intake of palatable food in mice

Pharmacol Biochem Behav. 2008 Nov;91(1):176-80. doi: 10.1016/j.pbb.2008.07.004. Epub 2008 Jul 19.

Abstract

(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.

MeSH terms

  • Amphetamine / pharmacology
  • Animals
  • Appetite Depressants*
  • Catecholamines / physiology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Drug Tolerance
  • Eating / drug effects*
  • Female
  • Food Preferences / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Pyrazines / pharmacology
  • Quinoxalines / pharmacology
  • Serotonin 5-HT2 Receptor Agonists*
  • Serotonin Receptor Agonists / pharmacology*
  • Tetrahydronaphthalenes / pharmacology*

Substances

  • 8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino(1,2-a)quinoxalin-5(6H)-one
  • Appetite Depressants
  • Catecholamines
  • Pyrazines
  • Quinoxalines
  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin Receptor Agonists
  • Tetrahydronaphthalenes
  • 1-phenyl-3-dimethylamino-1,2,3,4-tetrahydronaphthalene
  • Amphetamine