Comparative studies of local anesthetic effects on artificial membranes and isolated cardiac tissues.
Drugs with local anesthetic properties like propranolol, tetracaine, lidocaine, procaine, induce concentration dependent potentials in artificial membranes. The size of the drug induced potential correlates with cardiodepressant activity, measured as decrease in force of contraction of guinea-pig atria and papillary muscles. Drugs inducing high potentials like propranolol and tetracaine, show low EC50 values in cardiac tissues. Propranolol in comparison to lidocaine diffuses more rapidly across the lipid membrane as derived from the time dependent decline in membrane potential and from radioactive tracer measurements. After application of a single drug concentration on cardiac tissues a longer time is required for propranolol to reach steady state than for example for lidocaine. Effects are higher at pH 9 than at pH 7 and 7.4, respectively. The results suggest that the site of action of propranolol primarily are cytoplasmic cell structures whereas that of lidocaine and procaine is the outer membrane surface.
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D008563:Membrane Lipids; D008567:Membranes, Artificial; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D010539:Permeability; D011343:Procaine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013748:Tetracaine / Q000494:pharmacology
D000779:Anesthetics, Local; D008563:Membrane Lipids; D008567:Membranes, Artificial; D013748:Tetracaine; D011343:Procaine; D008012:Lidocaine; D011433:Propranolol