Short-lasting, Competitive Neuromuscular Blocking Activity in a Series of Azobis-Arylimidazo-[1,2-a]-Pyridinium Dihalides

Abstract

SUCCINYLCHOLINE is the most commonly used neuromuscular blocking drug for relaxing skeletal muscles during surgery or electroconvulsive therapy. Its main advantages are rapid onset and brief duration of action. It has, however, serious defects in that it often causes marked postoperative pain in skeletal muscles because its depolarizing action causes an asynchronous contraction in muscle bundles before paralysis occurs; there is no convenient remedy for controlling the prolonged apnoea which occurs in individuals deficient in serum pseudocholinesterase. Competitive neuromuscular blocking drugs such as (+)-tubocurarine or pancuronium do not cause muscle pain but are rather long-acting. Further disadvantages are that pancuronium has a slow onset of action and (+)-tubocurarine releases histamine and partially blocks autonomic ganglia at paralysing doses. There is therefore still a need for a short-acting, competitive neuromuscular blocking agent with a rapid onset of action and which does not affect the cardiovascular system at therapeutic doses. Some of the azobis-arylimidazo-[1,2-a]-pyridinium derivatives described here appear to have these properties. Most of the compounds were made by Glover¹ and his colleagues at Tees-side Polytechnic; some were made in the research laboratories of Allen and Hanburys Ltd. The compounds were prepared as dibromides or dichlorides. The reference drugs used were (+)-tubocurarine dichloride, succinylcholine dichloride, gallamine triethiodide and pancuronium dibromide. Here doses refer to the parent base.