Effects of the oral hypoglycemic agent methyl palmoxirate on exercise capacity of rats

The effect of the oral hypoglycemic agent methyl palmoxirate (methyl 2-tetradecylglycidate, McN-3716), a selective inhibitor of long chain fatty acid oxidation, on the exercise capacity of normal rats was evaluated. Daily administration of 2.5 mg/kg for 7 days, or of a single dose of 10 mg/kg, of methyl palmoxirate did not affect the ability of rats to perform strenuous exercise of an intensity that caused exhaustion in less than 30 min. The ability to perform prolonged, moderately strenuous exercise of an intensity that could be maintained for more than 60 min was decreased slightly (17%) in the methyl palmoxirate treated rats. This effect appeared to be mediated by a significant reduction in initial liver glycogen content in the methyl palmoxirate treated rats. As a consequence, the methyl palmoxirate treated rats became hypoglycemic during prolonged exercise. Inhibition of fatty acid oxidation in skeletal muscle was minimal. Treatment with methyl palmoxirate protected against the development of exercise-induced ketosis. It appears that the liver is the major site of action of methyl palmoxirate when given in low dosage.