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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.
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]
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]
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]
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]