NADOLOL-GLIBENCLAMIDE INTERACTION - RELEVANCE TO CARBOHYDRATE-METABOLISM IN HYPERGLYCEMIC RATS

In the present study, hyperglycaemia was induced by intraperitoneal in jection of streptozotocin (65 mg/kg). Treatment with glibenclamide (GB ) in a dose of 0.45 or 0.9 mg/kg significantly decreased plasma glucos e 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 ad ministration 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-treat ment, In relevance to the effect of ND and GB interactions towards oth er aspects of carbohydrate metabolism, co-administration of the two dr ugs [ND (10 mg/kg)+GB (0.9 mg/kg)] failed to alter the increase in pla sma insulin level and the decrease in blood pyruvate and lactate level s induced by GB alone. Concerning liver glycogen, concurrent administr ation of the two drugs showed a synergistic effect upon its content (2 57%), while it was 186% for GB treatment, and 179% for ND alone compar ed to the hyperglycaemic control value. The data revealed that ND pote ntiates the hypoglycaemic effect of GB, so it is very important to con sider this potentiation when the usage of the combined drug regimens i s recommended. (C) 1996 The Italian Pharmacological Society