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Clinical data | |
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Other names | Chandonium iodide; HS-310 |
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Routes of administration | IV |
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Pharmacokinetic data | |
Bioavailability | 100% (IV)[ citation needed ] |
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Chemical and physical data | |
Formula | C26H46I2N2 |
Molar mass | 640.477 g·mol−1 |
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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. By blocking these receptors, it prevents acetylcholine from triggering muscle contraction, leading to muscle relaxation.
Candocuronium was clinically evaluated in India for providing skeletal muscle relaxation during surgery, facilitating tracheal intubation, and assisting with mechanical ventilation. [3] While it showed a rapid onset of action and a short duration in the body, 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 pancuronium. [1]
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 belongs to a series of mono- and bis-quaternary azasteroids. This approach used the rigid steroid skeleton as a spacer to hold two quaternary ammonium groups, which incorporate fragments resembling choline or acetylcholine, at a specific distance. [8]
The research program first produced HS-342, a bis-quaternary agent that was 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 can lead to undesirable autonomic side effects. [11] [12]
Although candocuronium itself did not achieve the desired clinical profile, researchers continued to modify its structure. These efforts led to the creation of dihydrochandonium (HS-626), an analog with a 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 spurred further research into other modifications of the androstane nucleus, particularly at the 3- and 16-positions, ultimately yielding other agents that were considered for clinical testing. [16] [17] [18] [19]
Finally candocuronium is recognized as the only drug to have been discovered and advanced to clinical trials within an Indian university. [20] [3]