Candocuronium iodide

Candocuronium iodide

Clinical data
Pregnancy category	Not applicable
Routes of administration	IV
ATC code	none
Legal status
Legal status	Discontinued from clinical development
Pharmacokinetic data
Bioavailability	100% (IV)
Identifiers
IUPAC name (4aS,4bR,8S,10aR,10bS,12aS)-1,1,10a,12a-tetramethyl-8-(1-methylpyrrolidin-1-ium-1-yl)-3,4,4a,4b,5,7,8,9,10,10b,11,12-dodecahydro-2H-naphtho[2,1-f]quinolin-1-ium diiodide
Synonyms	Chandonium iodide; HS-310
CAS Number	54278-85-2 Y
PubChem CID	71537
ChemSpider	64610 N
UNII	SC80GNP08C
ChEMBL	CHEMBL2106112 N
Chemical and physical data
Formula	C26H46I2N2
Molar mass	640.47 g/mol
3D model (JSmol)	Interactive image
SMILES [I-].[I-].C\53=C/C[C@@H]1[C@H](CC[C@]2([C@H]1CCC[N+]2(C)C)C)[C@@]3(C)CC[C@H]([N+]4(C)CCCC4)C/5
InChI InChI=1S/C26H46N2.2HI/c1-25-14-12-21(28(5)17-6-7-18-28)19-20(25)10-11-22-23(25)13-15-26(2)24(22)9-8-16-27(26,3)4;;/h10,21-24H,6-9,11-19H2,1-5H3;2*1H/q+2;;/p-2/t21-,22+,23-,24-,25-,26-;;/m0../s1 N Key:GGAGIPMNQXAXNH-XDMKMBKMSA-L N
NY (what is this?)

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).

The mono- and bis-quaternary azasteroid series of compounds to which candocuronium belongs are based on the same principle that led to aminosteroids such as pancuronium, vecuronium and rocuronium: use of the steroid skeleton to provide a somewhat rigid distance between the two quaternary ammonium centers, with appendages incorporating fragments of choline or acetylcholine. The discovery program initiated by Singh initially led to the synthesis of the bis-quaternary non-depolarizing agent HS-342 (4,17a-dimethyl-4,17a-diaza-D-homo-5α-androstane dimethiodide) that was equipotent with tubocurarine and with one-third its duration of action, but not suitable for further clinical evaluation. Modifications of the HS-342 structure led to two other notable agents, HS-347 and HS-310 (subsequently named chandonium, then candocuronium). HS-347 was equipotent with tubocurarine but exhibited considerable ganglion blocking activity; candocuronium appeared to be suitably placed for clinical trials following encouraging preclinical evaluations.