A comparison of the local anaesthetic effects of cationic, anionic, and neutral amphipathic agents in frog skeletal muscle.
Impermeant alkyl amphipathic agents reduced the excitability of frog twitch muscle fibers, indicating that local anaesthesia can be produced by perturbations within the external lamina of the sarcolemma. Cationic (n-alkyl trimethylammonium) and anionic (n-alkyl sulfonate) as well as permeant neutral (n-alkanol) agents have been compared with regard to their local anaesthetic potency. Small impermeant agents (fewer than six carbon atoms) alone were ineffective. Within each series the concentration required to reduce excitability was proportional to the length (hydrophobicity) of the hydrocarbon chain attached to the polar group. However, corresponding members of these three series of compounds differed considerably in their local anaethetic potency. Hence, charged groups as well as apolar moieties can influence local anaesthetic efficacy. The supra-additive character of the local anaesthesia produced by combining impermeant alkyl anions and cations indicates that these two types of amphipaths may produce their similar effects by perturbations at different membrane sites.
D000200:Action Potentials / Q000187:drug effects; D000438:Alcohols / Q000494:pharmacology; D000476:Alkanesulfonates / Q000494:pharmacology; D000779:Anesthetics, Local; D000818:Animals; D000838:Anions / Q000494:pharmacology; D001001:Anura; D002412:Cations / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects*; D011343:Procaine / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D013464:Sulfuric Acids / Q000494:pharmacology
D000438:Alcohols; D000476:Alkanesulfonates; D000779:Anesthetics, Local; D000838:Anions; D002412:Cations; D000644:Quaternary Ammonium Compounds; D013464:Sulfuric Acids; D011343:Procaine