Nadolol-glibenclamide interaction: relevance to carbohydrate metabolism in hyperglycaemic rats

In the present study, hyperglycaemia was induced by intraperitoneal injection of streptozotocin (65 mg/kg). Treatment with glibenclamide (GB) in a dose of 0.45 or 0.9 mg/kg significantly decreased plasma glucose level in a dose-related manner. Administration of nadolol (ND) in a dose of 5 or 10 mg/kg did not affect plasma glucose level. Combined administration of ND (10 mg/kg) with GB (0.45 or 0.9 mg/kg) potentiated the hypoglycaemic effect of GB, an effect prominent 4 hours post-treatment. In relevance to the effect of ND and GB interactions towards other aspects of carbohydrate metabolism, co-administration of the two drugs [ND (10 mg/kg) + GB (0.9 mg/kg)] failed to alter the increase in plasma insulin level and the decrease in blood pyruvate and lactate levels induced by GB alone. Concerning liver glycogen, concurrent administration of the two drugs showed a synergistic effect upon its content (257%), while it was 186% for GB treatment, and 179% for ND alone compared to the hyperglycaemic control value. The data revealed that ND potentiates the hypoglycaemic effect of GB, so it is very important to consider this potentiation when the usage of the combined drug regimens is recommended.