Metabolic profile of beta-adrenoceptor-blocking action of befunolol.
The present study was undertaken to elucidate the metabolic profile of the beta-blocking effects of befunolol on catecholamine-induced changes in plasma glucose, lactate and free fatty acid concentrations and myocardial metabolism. Effects of propranolol were also tested for the purpose of comparison. Epinephrine, at doses of 0.2 to 0.35 mg/kg, induced significant increases in the plasma glucose, lactate and free fatty acid concentrations. These changes were inhibited by pretreatment with either befunolol or propranolol at doses of 0.03 mg/kg or above. Isoproterenol-induced changes in systemic blood pressure and heart rate were reduced by pretreatment with intravenous injection of 10 and 100 micrograms/kg of bufunolol and 100 micrograms/kg of propranolol. Isoproterenol-induced changes in myocardial ATP, creatine phosphate, lactate and cyclic AMP were also reduced by pretreatment with 10 and 100 micrograms/kg of befunolol and 100 micrograms/kg of propranolol. Propranolol, at a dose of 10 micrograms/kg, did not reduce isoproterenol-induced changes in heart rate, blood pressure, and in myocardial ATP, creatine phosphate and cyclic AMP contents. The results demonstrate that befunolol exerts an inhibitory action on catecholamine-induced hemodynamic and metabolic alterations, and provide further evidence for the beta-blocking action of this drug.
Department of Pharmacology, Tokyo College of Pharmacy, Japan.
Y
Y
Maruyama
T
T
Awaji
M
M
Inoue
S
S
Takeo
D000255:Adenosine Triphosphate / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D007773:Lactates / Q000097:blood / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007773:Lactates; D011412:Propanolamines; D010725:Phosphocreatine; C006034:befunolol; D000255:Adenosine Triphosphate; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol