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Candocuronium iodide
Chemical compound From Wikipedia, the free encyclopedia
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Candocuronium iodide (INN; formerly chandonium iodide or HS-310)[1] is an aminosteroid neuromuscular-blocking drug that was investigated as a muscle relaxant for use in anesthesia. It acts as a competitive antagonist of the nicotinic acetylcholine receptor at the neuromuscular junction.[2] By blocking these receptors, it prevents acetylcholine from triggering muscle contraction, leading to muscle relaxation.
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Medical use and discontinuation
Candocuronium was clinically evaluated in India for providing skeletal muscle relaxation during surgery, facilitating tracheal intubation, and assisting with mechanical ventilation.[3] According to Talukdar and Sarkar, it showed a rapid onset of action and a short duration in the body, but its development was halted due to cardiovascular side effects, particularly tachycardia.[3] Several studies suggested, however, that the severity of these effects was similar to that of the clinically established neuromuscular blocker, pancuronium bromide.[4][5][6][7] Candocuronium was also noted to have little to no ganglion-blocking activity and greater potency than of pancuronium.[1]
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History and development
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Rationale and design
The drug was developed in the laboratory of Harkishan Singh at Panjab University as part of a research program seeking a non-depolarizing neuromuscular blocker to replace the widely used depolarizing agent suxamethonium (succinylcholine).[8] The design of candocuronium places it in a series of mono- and bis-quaternary azasteroids. The approach adopted in its development used the rigid steroid skeleton as a spacer to hold two quaternary ammonium groups (inspired by the alkaloid malouetine), which incorporate fragments resembling choline or acetylcholine, at a specific distance.[8]
Synthesis and early analogs
The research program first produced HS-342, a bis-quaternary agent that was reportedly equipotent with tubocurarine and had one-third its duration of action. However, it was deemed unsuitable for further clinical evaluation.[9][10]
Subsequent chemical modifications of HS-342 led to the synthesis of two related derivatives: HS-310 (later named candocuronium) and HS-347.[1][8] HS-347, though equipotent with tubocurarine, was precluded from clinical trials because it exhibited considerable ganglion-blocking activity, which potentially leads to undesirable autonomic side effects.[11][12]
Further modifications and legacy
H-310 did not achieve the desired clinical profile, which led to the continued modification of its structure, ultimately resulting in the creation of dihydrochandonium (HS-626). The new variant was an analog with a reported slightly improved neuromuscular blocking profile and no vagolytic effects.[13][14] However, this benefit was not considered significant enough to advance the compound to human trials.[15]
The discovery of candocuronium prompted further research into modifications of the androstane nucleus, particularly at the 3- and 16-positions, leading to the development of other agents considered for clinical testing.[16][17][18][19]
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References
External links
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