Effect of a New Hypoglycemic Agent, 3,5-Dimethylpyrazole, on Carbohydrate and Free Fatty Acid Metabolism

Abstract

As a hypoglycemic agent, 3,5-dimethylpyrazole (U-6245) was found to be fifty-four times more potent orally than tolbutamide in glucose-injected, fasted intact rats. U-6245 increased glucose oxidation by intact rats. It lowered plasma free fatty acids but not blood sugar of eviscerate rats and was effective in decreasing the fasting bloodsugar levels of alloxan-diabetic rats which were unresponsive to tolbutamide. U-6245 markedly depressed plasma FFA fifteen minutes to three hours after its administration. The mechanism of hypoglycemic activity of 3,5-dimethylpyrazole is not the same as insulin, sulfonylureas or biguanides in that: (1) It is ineffective in lowering the blood sugar of eviscerates while insulin is. (2) U-6245 is active in alloxan diabetic rats which are unresponsive to tolbutamide. (3) The pyrazole increases glucose oxidation and biguanides do not. Although the mechanism of action of 3,5-dimethylpyrazole is not understood, data are presented which support the hypothesis that its action may depend on its effect on plasma FFA and also on the presence of the liver and/or intestinal tract. Since the pyrazole increases glucose oxidation in intact rats, it appears that at least part of its action may be due to the stimulation of glucose oxidation by the intestinal tract and/or liver.