A new class of peripherally acting anorectics is described in these studies. The four stereoisomers of chlorocitric acid which are structurally similar to the known anorectic, (--)-threo-hydroxycitric acid, all suppressed food intake when administered at high doses to rats. Only one of these isomers, (--)-threo-chlorocitric acid, retained its anorectic activity at lower doses. The anorectic potency of (--)-threo-chlorocitric acid was approximately 40-fold greater in dogs than in lean and obese rats. The decreased food intake in rats resulted in a significant reduction of body lipid, without affecting protein levels. In contrast to the tolerance which was observed with the continued administration of mazindol or diethylpropion, tolerance to the anorectic effect of (--)-threo-chlorocitric acid did not develop. These studies suggest that (--)-threo-chlorocitric acid might be useful as an antiobesity agent.

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http://dx.doi.org/10.1016/0091-3057(81)90192-1DOI Listing

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