Effects of the appetite stimulant chlordimeform on food and water consumption of rats: comparison with chlordiazepoxide
Witkin, J.M.; Leander, J.D.
Journal of Pharmacology and Experimental Therapeutics 223(1): 130-134
1982
ISSN/ISBN: 0022-3565 PMID: 7120114 Document Number: 195382
Chlordimeform (N'-(4-chloro-o-tolyl)N,N-dimethylformamidine) and chlordiazepoxide were administered to non-food-deprived rats in doses of 1.25-40.0 mg/kg (i.p.) 30 min before a 1-h period of access to food or water. Both compounds (2.5-10.0 mg/kg) increased food intake. As is typical of most compounds which increase food intake, chlordiazepoxide (2.5-10.0 mg/kg) also increased water consumption of 23-h water-deprived rats; chlordimeform produced only dose-related decreases in water consumption. The water intake dose-response function for chlordimeform was shifted to the right when food was available during the drinking session, suggesting the occurrence of prandial drinking (drinking associated with eating); the chlordiazepoxide dose-effect function was not affected by food availability. Combinations of chlordimeform and chlordiazepoxide produced effects on water consumption that were similar to those produced by chlordimeform alone, suggesting that chlordimeform and chlordiazepoxide affect drinking via different mechanisms. Water intake of non-water-deprived rats was also increased by chlordiazepoxide (5.0 mg/kg), but it was not increased by chlordimeform (1.25-20.0 mg/kg). d-Amphetamine (0.1-3.0 mg/kg i.p., 10 min presession) decreased water consumption. Food intake was decreased by d-amphetamine, indicating that food intake was not indiscriminately increased by administration of drugs which decrease water consumption (i.e., chlordimeform). Chlordimeform affected food and water consumption at doses well below lethal values (LD50 = 160 mg/kg i.p.). Administration of the higher doses of chlordiazepoxide (10.0 and 20.0 mg/kg) produced sedation, muscle relaxation and ataxia. Chlordimeform (40.0 mg/kg) produced muscle rigidity and signs of sympathetic activation. As an appetite stimulant, chlordimeform possesses novel pharmacological properties.