The antiobesity action of (S)-(+)-1-(4-chlorophenylthiomethyl)-N-methylethylamine fumarate (AO-124).

Abstract

The antiobesity effects of (S)-(+)-1-(4-chlorophenylthiomethyl)-N-methylethylamine fumarate (AO-124) were examined in rats and dogs. AO-124 suppressed food intake dose dependently in normal, Zucker fatty and VMH-obese rats, and beagle dogs. Its anorectic activity was not altered by pretreatment with methysergide, a serotonin receptor blocker. AO-124 also reduced the hyperphagia induced by 2-deoxy-D-glucose but not that induced by insulin, noradrenaline or muscimol, suggesting that the anoretic mechanism of AO-124 may be implicated in a glucostatic regulatory system of feeding. In addition, AO-124 decreased insulin secretion in response to an oral, but not an intravenous, glucose load. Such a suppression in insulin secretion may be explained by slow absorption of glucose from the intestine: AO-124 delayed the gastric emptying time of glucose and inhibited the active transport of glucose as observed in the everted small intestine. Two week administration of AO-124 to Zucker fatty rats resulted in a significant reduction of plasma insulin levels, body weight gain, and body lipid without exerting any changes in body protein. These findings indicate that AO-124 may be useful as an antibesity agent on the basis of its unique mechanisms of action.

Cite this paper

@article{Ikeda1986TheAA, title={The antiobesity action of (S)-(+)-1-(4-chlorophenylthiomethyl)-N-methylethylamine fumarate (AO-124).}, author={Hitoshi Ikeda and K. Shimakawa and Gakushi Kito and Kenichi Meguro and Toshihiko Matsuo}, journal={European journal of pharmacology}, year={1986}, volume={125 2}, pages={201-10} }