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THE INTERACTION OF AMINE LOCAL ANAESTHETICS WITH MUSCARINIC RECEPTORS
Author(s) -
TAYLOR W.J.,
WOLF A.,
YOUNG J.M.
Publication year - 1980
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1980.tb10943.x
Subject(s) - tetracaine , prilocaine , chemistry , carbachol , muscarinic acetylcholine receptor , procaine , dibucaine , acetylcholine , acetylcholine receptor , receptor , local anesthetic , pharmacology , anesthesia , endocrinology , biochemistry , lidocaine , biology , medicine
1 Amine local anaesthetics inhibited the binding of (‐)‐[ 3 H]‐quinuclidinyl benzilate ((‐)‐[ 3 H]‐QNB) to muscarinic receptors in crude synaptosomal preparations from guinea‐pig brain. The order of potency was SKF 525A > tetracaine > procaine ⋍ quinidine > procainamide > bupivacaine > lignocaine > prilocaine. 2 The concentration of tetracaine or prilocaine causing 50% inhibition of the receptor‐specific binding of [ 3 H]‐QNB varied linearly with the concentration of [ 3 H]‐QNB present for the range of concentrations of prilocaine used and at lower concentrations of tetracaine, thus providing evidence for a competitive interaction. The affinity constant for tetracaine was 2.6 ± 0.2 × 10 5 m −1 and that for prilocaine 2.6 ± 0.8 × 10 3 m −1 . At higher concentrations of tetracaine the interaction appears to diverge from simple competitive kinetics. 3 The log dose‐response curve for the contractile response of longitudinal muscle strips from guinea‐pig intestine to carbachol was shifted in a parallel fashion by low concentrations of tetracaine, but flattened by higher doses. A similar effect was observed for both lignocaine and prilocaine. The affinity constants for tetracaine and prilocaine calculated from the parallel shifts, 1 × 10 5 m −1 and 4 × 10 3 m ‐1 , respectively, were in reasonable accord with the binding data. 4 The curve for the inhibition of [ 3 H]‐QNB binding by carbachol was not significantly altered, either in position or shape, in the presence of 1 m m prilocaine. Thus there is no evidence that prilocaine, which increases the affinity of nicotinic acetylcholine receptors for agonists, has any similar effect on agonist binding to muscarinic receptors.