Studies on the mechanism of action of a novel anorectic agent, (--)-threo-chlorocitric acid.

(--)-threo-Chlorocitric acid, a novel and potent anorectic agent in rats and dogs, decreased food intake to a comparable extent in rats fed chow, low fat, or high fat diets. This inhibition of food intake was not the result of conditioned aversion. Unlike (--)-threo-hydroxycitric acid, a structurally related compound which inhibits fatty acid synthesis, (--)-threo-chlorocitric acid did not suppress fatty acid synthesis in an isolated hepatocyte system or in vivo. (--)-threo-Chlorocitric acid significantly delayed the rate of gastric emptying. Of the four stereoisomers of chlorocitric acid, (--)-threo-chlorocitric acid was the most active both in delaying gastric emptying and producing anorexia in rats. It is suggested that the mechanism by which (--)-threo-chlorocitric acid may suppress food intake is through a reduction of gastric emptying.