Some Effects of 1-Methyl-4-(3-Methyl-5-Isoxazolyl) Pyridinium Chloride and Phenformin on Carbohydrate and Lipid Metabolism in Mice

1-Methyl-4-(3-methyl-5-isoxazolyl)pyridiniuni chloride (I) was previously reported to be a potent oral hypoglycemic agent in normal and alloxan diabetic animals. The present studies were undertaken to define the effects of I on carbohydrate and lipid metabolism. A comparison with phenformin was also made. Hypoglycemia induced in mice after acute or chronic administration of I was associated with increased skeletal muscle glycogen concentration and lactacidemia. Hepatic glycogen decreased after a single dose of I while increased or unaltered liver glycogen concentration was observed after chronic treatment. The data suggest that compound I may cause hypoglycemia in mice by increasing the uptake of glucose by skeletal muscle. Hypoglycemia, unaltered hepatic glycogen and increased blood lactate and muscle glycogen concentration were observed after a single oral dose of phenformin. Hepatic and plasma triglyceride, sterol and phospholipid levels were unaltered after chronic treatment with I. Phenformin induced a decrease in plasma triglyceride while plasma sterol and phospholipid and liver lipids were unchanged after chronic treatment. These data suggest that I may have clinical utility as an oral hypoglycemic agent.