Frequency-dependent block of nerve conduction by beta-adrenergic blocking agents.
We investigated frequency-dependent effects of 12 beta-adrenergic blocking agents, all 1-aryloxy-3-isopropylaminopropane-2-ol derivatives, on the height of the compound action potential of frog sciatic nerves, using sucrose gap techniques. The order of 1/ED50 of these agents at 0.1 Hz for the reduction of the height was: indenolol greater than D-25 greater than propranolol greater than alprenolol greater than pindolol greater than toliprolol greater than oxprenolol greater than befunolol greater than Kö1313 greater than acebutolol greater than metoprolol greater than atenolol. The order was similar also at 100 Hz. Logarithms of n-octanol/buffer partition coefficients (log P) correlated well with log (1/ED50) at either 0.1, 1, 10 or 100 Hz (p less than 0.01). The order of log [(ED50)0.1 Hz/(ED50)100 Hz] was oxprenolol greater than befunolol greater than propranolol greater than alprenolol greater than toliprolol greater than indenolol greater than Kö1313 greater than pindolol greater than D-25. Molecular weight of these drugs correlated well with the difference of log (ED50)100 Hz and log (ED50)10 Hz from log (ED50)0.1 Hz (P less than 0.05). The results indicate that the local anesthetic potency of these beta-blockers is mainly determined by the lipid solubility of the drugs, being modified by the frequency-dependent component of action which is related to the molecular weight.
D000200:Action Potentials / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008970:Molecular Weight; D009412:Nerve Fibers / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects*; D011892:Rana catesbeiana; D012044:Regression Analysis; D012964:Sodium / Q000378:metabolism; D012995:Solubility
D000319:Adrenergic beta-Antagonists; D007473:Ion Channels; D012964:Sodium