Dose difference in beta-adrenergic blockers with intrinsic sympathomimetic action to block beta-adrenoceptors and induce sympathomimetic action.
1. Isoprenaline, a beta-adrenergic full agonist, and carteolol, befunolol and BFE-55, beta-adrenergic blockers with an intrinsic sympathomimetic action, induced dose-related increases in heart rate when administered intravenously (i.v.). 2. The beta-partial agonists administered i.v. shifted a dose-heart rate increased response curve of isoprenaline, suggesting a competitive antagonism. 3. In carteolol, doses to block beta-adrenoceptors were found to be 400-1000 times lower than that to induce agonistic action. In BFE-55, doses to block beta-adrenoceptors were equal to that to induce sympathomimetic action. The difference between doses of the befunolol to produce both actions was intermediate. 4. These results suggest that there may be a difference between doses blocking beta-adrenoceptors and inducing sympathomimetic action in some beta-adrenergic partial agonists and, therefore, that there may exist beta-partial agonists which do not induce sympathomimetic action in doses blocking beta-adrenoceptors.
Takayanagi
I
I
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Ogishima
M
M
Koike
K
K
Hisayama
T
T
Hayashida
M
M
Fujii
M
M
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002354:Carteolol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013566:Sympathomimetics / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D013566:Sympathomimetics; C052295:BFE 55; C006034:befunolol; D002354:Carteolol; D007545:Isoproterenol