Candocuronium iodide (INN, formerly chandonium, HS-310) is an aminosteroid neuromuscular-blocking drug or skeletal muscle relaxant in the category of non-depolarizing neuromuscular-blocking drugs. Its potential adjunctive use in anesthesia to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation was briefly evaluated in clinical studies in India, but further development discontinued because of attendant cardiovasular effects, primarily tachycardia that was no worse than but also not an improvement over the clinically established pancuronium bromide. Candocuronium demonstrated a short duration and a rapid onset of action, with little or no ganglion blocking activity, and it was only slightly less potent than pancuronium.
As with other neuromuscular blocking agents, candocuronium preferentially antagonizes competitively the nicotinic subtype of acetylcholine receptors. The agent was developed by the laboratory of Harkishan Singh, Panjab University, Chandigarh, India, as part of the search for a non-depolarizing replacement for the most popular clinically used depolarizing agent, suxamethonium (succinylcholine).
However, candocuronium did not provide the desired profile,[clarification needed] and a further extension of research was undertaken to overcome its limitations.[clarification needed] This led to four more promising compounds,[editorializing] HS-692, HS-693, HS-704 and HS-705,[clarification needed] whose onset and duration were indinguishable from candocuronium, but, unfortunately,[editorializing] all demonstrated profound vagolytic effects and much weaker potencies than candocuronium. To improve on potency, further modifications of the candocuronium nucleus were undertaken,[clarification needed] leading to the identification of yet another promising compound,[editorializing] HS-626. Unfortunately, upon further preclinical evaluation in the cat and isolated preparations, HS-626 demonstrated a slightly more desirable neuromuscular blocking profile than that of candocuronium, but its overall improvement was insufficient to warrant advancement to clinical testing.
The discovery of candocuronium led to numerous related neuromuscular blocking agents with short durations of action but also having attendant undesirable cardiovascular effects. The Marshall group then explored other modifications at the 3- and 16-positions of the androstane nucleus, but the work has not yet yielded an agent worthy of expanded evaluation to clinical testing in this azasteroidal class of neuromuscular blocking agents.
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^ Suri YV (1984). Chandonium-iodide. New non-depolarising muscle relaxant. In: "Anaesthesiology. Clinical Pharmacology" Suri YV, Singh D (Eds.) New Delhi: Vani Educational Books; 28-35.
^ Harvey AL, Paul D, Rodger IW, Singh H (1976). "Actions of the muscle relaxant chandonium iodide on guinea-pig ileum and vas deferens preparations". J Pharm Pharmacol. 28 (8): 617–619. doi:10.1111/j.2042-7158.1976.tb02812.x. PMID 11309.
^ a b Singh H, Paul D (1974). "Steroids and related studies. XXV. Chandonium iodide (17a-methyl-3beta-pyrrolidino-17a-aza-D-homoandrost-5-ene dimethiodide) and other quaternary ammonium steroid analogues". J Chem Soc Perkin 1. 12: 1475–1479. doi:10.1039/p19740001475. PMID 4472321.
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^ Marshall IG, Paul D, Singh H (May 1973). "The neuromuscular and other blocking actions of 4,17a-dimethyl-4,17a-diaza-d-homo-5 -androstane dimethiodide (HS-342) in the anaesthetized cat". Eur J Pharmacol. 22 (2): 129–134. doi:10.1016/0014-2999(73)90002-2. PMID 4715215.
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^ Singh H, Bhardwaj TR, Ahuja NK, Paul D (1979). "Steroids and Related Studies. Part 44. 17a-Methyl-3β-(N-pyrrolidinyl)-17a-aza-D-homo-5α-androstane Bis(methiodide) (Dihydrochandonium Iodide) and Certain Other Analogues of Chandonium Iodide". J. Chem. Soc. Perkin Trans. 1: 305.
^ Singh H, Bhardwaj TR, Paul D (1979). "Steroids and Related Studies. Part 48. A Chandonium Iodide Analogue possessing an Acetylcholine-like Moiety". J. Chem. Soc. Perkin Trans. 1: 2451.
^ Marshall IG, Harvey AL, Singh H, Bhardwaj TR, Paul D (Jul 1981). "The neuromuscular and autonomic blocking effects of azasteroids containing choline or acetylcholine fragments". J Pharm Pharmacol. 33 (7): 451–457. doi:10.1111/j.2042-7158.1981.tb13831.x. PMID 6115032.
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^ Jindal DP, Piplani P, Fajrak H, Prior C, Marshall IG (Nov 2002). "Synthesis and neuromuscular blocking activity of 16β-N-methylpiperazino steroidal derivatives". Eur J Med Chem. 37 (11): 901–908. doi:10.1016/s0223-5234(02)01413-7. PMID 12446049.