Metabolic fate of the short-acting peripheral neuromuscular blocking agent stercuronium in the rat, as related to its action

Among a number of synthetic derivatives of conessine, a steroid of natural origin, the mono-quaternary compound conessine ethoiodide (stercuronium) was outstanding as a very short-acting neuromuscular blocking agent of the non-depolarizing type. After intravenous administration of [ 14C]labelled stercuronium the short duration of action was found to be directly related to the rapid decline of the blood level below a critical concentration. During the neuromuscular blockade, excretion of radioactivity in urine and bile, although substantial, was still too small to explain the rapid decline of the blood level. Whole-body autoradiography showed rapid uptake of stercuronium radioactivity in liver and kidneys to be the main factor determining the short action. Both excretion and distribution studies show prolonged retention of part of the administered radioactivity dose in the organism. Excretion data obtained for some rats reveal different half-lives for the urinary and biliary excretion of radioactivity, which suggests the existence of at least two separate storage pools. Judging from the long-term distribution studies, these pools are probably located in the liver and kidneys. Analytical studies gave no evidence for biotransformation of stercuronium in the rat.