THE INTERACTION OF AMINE LOCAL ANAESTHETICS WITH MUSCARINIC RECEPTORS

Abstract

1 Amine local anaesthetics inhibited the binding of (-)-[3H]-quinuclidinyl benzilate ((-)-[3H]-QNB) to muscarinic receptors in crude synaptosomal preparations from guinea-pig brain. The order of potency was SKF 525A greater than tetracaine greater than procaine congruent to quinidine greater than procainamide greater than bupivacaine greater than lignocaine greater than prilocaine. 2 The concentration of tetracaine or prilocaine causing 50% inhibition of the receptor-specific binding of [3H]-QNB varied linearly with the concentration of [3H]-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 x 10(5) M-1 and that for prilocaine 2.6 +/- 0.8 x 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 x 10(5) M-1 and 4 x 10(3) M-1, respectively, were in reasonable accord with the binding data. 4 The curve for the inhibition of [3H]-QNB binding by carbachol was not significantly altered, either in position or shape, in the presence of 1 mM 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.