Metabolic actions of a single atenolol and metoprolol dose.
Atenolol (CAS 29122-68-7) and metoprolol (CAS 37350-58-6) are beta 1-selective adrenoceptor antagonists without intrinsic sympathomimetic activity. beta-Receptor blockers influence carbohydrate- and lipid metabolism. Liver is a central organ of these processes. The metabolic fate of a single oral atenolol and metoprolol dose and their actions on carbohydrate- and lipid parameters have been investigated. Healthy male rats received a dose reducing heart beat/min by 25% (atenolol: 6 mg/kg; metoprolol: 10 mg/kg). About 9% of atenolol is metabolized by cytochrome P-450 (P-450). P-450-dependent functions (aminopyrine-N-demethylase, hexobarbital biotransformation time) were not inhibited. Serum bilirubin was normal. Triglyceride (TG), total cholesterol and HDL-cholesterol levels of the plasma were not affected. Transient blood glucose increase was measured returning to initial value at 120 min. Metoprolol is metabolized by hepatic monooxygenases. P-450-dependent functions were inhibited correlating to the lowered P-450-content of the microsomes. High TG level and decreased HDL-cholesterol content were measured. Blood glucose was significantly high. The liposoluble metroprolol affected the hepatic functions more than the hydrophilic atenolol. The monitoring of blood glucose during beta-receptor antagonist treatment may be suggested.
Department of Pharmacology, University Medical School, Debrecen, Hungary.
J
J
Kulcsár-Gergely
E
E
Pósán
A
A
Kulcsár
D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D001663:Bilirubin / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002784:Cholesterol / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006591:Hexobarbital / Q000493:pharmacokinetics; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008660:Metabolism / Q000187:drug effects*; D008790:Metoprolol / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D014280:Triglycerides; D001262:Atenolol; D002784:Cholesterol; D006591:Hexobarbital; D006899:Mixed Function Oxygenases; D008790:Metoprolol; D001663:Bilirubin