INTERACTION OF DECAMETHONIUM WITH HEXAMETHONIUM OR VECURONIUM IN THE RAT - AN ISOBOLOGRAPHIC ANALYSIS

We used isobolographic analysis to investigate the interaction of deca methonium with either hexamethonium or vecuronium in the rat phrenic n erve hemidiaphragm preparation. EC(50) values of decamethonium, hexame thonium, and vecuronium were (mean +/- SEM) 47.36 +/- 9.58 mu M, 4.27 +/- 0.53 mM, and 5.19 +/- 1.17 mu M, respectively. Combinations of dru gs in concentrations corresponding to the 1:2, 1:1, and 2:1 ratios of their EC(50) values were used to determine three points of each isobol e. Decamethonium and hexamethonium showed antagonism: significant devi ations from the line of additivity were found at EC(50) ratios of 2:1 and 1:1 (P < 0.01 and P < 0.05, respectively) indicating that hexameth onium is a potent antagonist of decamethonium. For decamethonium and v ecuronium none of the three points on the isobole was significantly di fferent from the corresponding point on the line of additivity. Hexame thonium is known to be a weak antagonist at the postsynaptic nicotinic acetylcholine receptor but a potent antagonist at the presynaptic nic otinic receptor. Vecuronium is a more potent antagonist at the postsyn aptic nicotinic receptor but a much weaker antagonist at the presynapt ic site. It was postulated that in the rat the primary site of action of decamethonium is at the presynaptic nerve terminal. Our findings su ggest that presynaptic rather than postsynaptic potency of a nondepola rizing drug determines ability to antagonize the effect of a depolariz ing drug in the rat.