Succinylcholine: still beautiful and mysterious after all these years

Abstract

To celebrate 30 years of publication of the Journal (1, 2), we comment on another amazing drug, which has stood the test of time: the muscle relaxant succinylcholine. The story of succinylcholine (or suxamethonium) should perhaps begin with the Amazonian and other aboriginal peoples. Few of us have failed to be mesmerized by their ability to hunt successfully with flimsy arrows, tipped with extracts of various species of Strychnos and Chondrodendron. The efficiency with which the arrows fell prey is due to the fast muscle-paralysis brought about by d-tubocurarine, present in the concentrated extracts, often potentiated with venom. Physicians rationalized that the muscle relaxation and paralysis induced by curare, could perhaps be put to good use for the treatment of tetanus, epilepsy and spastic disorders. Indeed by the 19th century, curare was already part of Western medicine with the celebrated Claude Bernard as one of the main investigators. By 1942, curare was already well established in general anaesthesia (3). The introduction and wide adoption of electro-convulsive therapy (ECT) for depression, and the efficacy of curare in minimizing the incidence of fractures and dislocations during ECT, lead to increasing demand for the muscle relaxant (4). A synthetic alternative was therefore sought. Succinylcholine was first, successfully and simultaneously, synthesized in 1949, by three independent groups in Italy, Great Britain and the United States. Particularly interesting was Barlow’s, synthesis of the depolarizing agent, as part of his undergraduate research project (5, 6). The close structural similarities between acetylcholine and succinylcholine are shown in Fig. 1. In designing succinylcholine, Barlow and Ing, his supervisor (6), in fact attempted to replicate the two positively charged amino centres in the d-tubcurarine structure, once mistakenly thought to be two quaternary ammonium centres (Fig. 1).