Candocuronium iodide

From Wikipedia, the free encyclopedia
(Redirected from Chandonium)

Template:Short description Template:Cs1 config

Page Module:Message box/ambox.css has no content.Page Template:Multiple issues/styles.css has no content.

Template:Short description Page Template:Infobox drug/styles.css has no content.

Page Module:Infobox/styles.css has no content.

Candocuronium iodide
Lua error in package.lua at line 80: module 'Module:InfoboxImage/data' not found.
Clinical data
Other namesChandonium iodide; HS-310
Pregnancy
category		Page Template:Plainlist/styles.css has no content.
  • Not applicable
Routes of
administration		IV
ATC codePage Template:Plainlist/styles.css has no content.
  • none
Legal status
Legal statusPage Template:Plainlist/styles.css has no content.
  • Discontinued from clinical development
Pharmacokinetic data
Bioavailability100% (IV)[citation needed]
Identifiers
  • (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
CAS NumberPage Template:Plainlist/styles.css has no content.
PubChem CIDPage Template:Plainlist/styles.css has no content.
PubChem SIDPage Template:Plainlist/styles.css has no content.
IUPHAR/BPSPage Template:Plainlist/styles.css has no content.
DrugBankPage Template:Plainlist/styles.css has no content.
ChemSpiderPage Template:Plainlist/styles.css has no content.
UNIIPage Template:Plainlist/styles.css has no content.
KEGGPage Template:Plainlist/styles.css has no content.
ChEBIPage Template:Plainlist/styles.css has no content.
ChEMBLPage Template:Plainlist/styles.css has no content.
NIAID ChemDBPage Template:Plainlist/styles.css has no content.
PDB ligandPage Template:Plainlist/styles.css has no content.
CompTox Dashboard (EPA)Page Template:Plainlist/styles.css has no content.
Chemical and physical data
FormulaC26H46I2N2
Molar mass640.477 g·mol−1
3D model (JSmol)Page Template:Plainlist/styles.css has no content.
  • [I-].[I-].C53=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=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
Data page
Template:Infobox drug/data page link
Page Template:Nobold/styles.css has no content. ☒NcheckY (what is this?)Page Template:Nobold/styles.css has no content.  (verify)

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 by blocking the binding 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.

Medical use and discontinuation

Candocuronium was clinically evaluated in India for providing skeletal muscle relaxation during surgery, easing tracheal intubation, and assisting with mechanical ventilation.[3] Clinical studies reported a rapid onset of action with a short duration. Development was discontinued due to cardiovascular side effects, notably tachycardia.[3] Several studies suggested that the severity of these effects were similar to that of the clinically established neuromuscular blocker, pancuronium bromide.[4][5][6][7] Research indicated that candocuronium had minimal ganglion-blocking activity and higher potency than pancuronium.[1]

History and development

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 azasteroid. 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 would potentially lead 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, and was reported to be a slightly better neuromuscular blocking profile and had 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]

References

Page Template:Reflist/styles.css has no content.

  1. ^ a b c Page Module:Citation/CS1/styles.css has no content.Gandiha A, Marshall IG, Paul D, Singh H (Nov 1974). "Neuromuscular and other blocking actions of a new series of mono and bisquaternary aza steroids". The Journal of Pharmacy and Pharmacology. 26 (11): 871–877. doi:10.1111/j.2042-7158.1974.tb09195.x. PMID 4156557. S2CID 37704229.
  2. ^ Page Module:Citation/CS1/styles.css has no content.Harvey AL, Paul D, Rodger IW, Singh H (Aug 1976). "Actions of the muscle relaxant chandonium iodide on guinea-pig ileum and vas deferens preparations". The Journal of Pharmacy and Pharmacology. 28 (8): 617–619. doi:10.1111/j.2042-7158.1976.tb02812.x. PMID 11309. S2CID 7700031.
  3. ^ a b Page Module:Citation/CS1/styles.css has no content.Talukdar A, Sarkar D (August 2023). "Catalyzing the Future of Medicinal Chemistry Research in India". Journal of Medicinal Chemistry. 66 (16): 10868–10877. doi:10.1021/acs.jmedchem.3c01304. PMID 37561395.
  4. ^ Page Module:Citation/CS1/styles.css has no content.Dasgupta D, Gupta KC, Vispute AV, Karandikar SM (Apr 1990). "Comparative clinical evaluation of chandonium iodide and pancuronium bromide as muscle relaxant". Journal of Postgraduate Medicine. 36 (2): 95–99. PMID 2151453.
  5. ^ Page Module:Citation/CS1/styles.css has no content.Dasgupta D, D'Souza M, Shah SJ, Gupta KC, Satoskar RS (Mar 1988). "Clinical evaluation of chandonium iodide as muscle relaxant". The Indian Journal of Medical Research. 87: 298–302. PMID 3397166.
  6. ^ Page Module:Citation/CS1/styles.css has no content.Kumar D, Bhatia VK, Yajnik S, Gaur SP, Nityanand S (Oct 1990). "Clinical evaluation of chandonium iodide as a nondepolarising muscle relaxant". The Indian Journal of Medical Research. 92: 367–370. PMID 2148735.
  7. ^ 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.
  8. ^ a b c Page Module:Citation/CS1/styles.css has no content.Singh H, Paul D (1974). "Steroids and related studies. Part XXV. Chandonium iodide (17a-methyl-3β-pyrrolidino-17a-aza-D-homoandrost-5-ene dimethiodide) and other quaternary ammonium steroid analogues". Journal of the Chemical Society, Perkin Transactions 1. 0 (12): 1475–1479. doi:10.1039/p19740001475. PMID 4472321.
  9. ^ Page Module:Citation/CS1/styles.css has no content.Marshall IG, Paul D, Singh H (Jun 1973). "Some actions of 4,17a-dimethyl-4,17a-diaza-D-homo-5alpha-androstane dimethiodide (HS-342), a new neuromuscular blocking drug". The Journal of Pharmacy and Pharmacology. 25 (6): 441–446. doi:10.1111/j.2042-7158.1973.tb09130.x. PMID 4146581. S2CID 46013073.
  10. ^ Page Module:Citation/CS1/styles.css has no content.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". European Journal of Pharmacology. 22 (2): 129–134. doi:10.1016/0014-2999(73)90002-2. PMID 4715215.
  11. ^ Page Module:Citation/CS1/styles.css has no content.Gandiha A, Marshall IG, Paul D, Rodger IW, Scott W, Singh H (Mar–Apr 1975). "Some actions of chandonium iodide, a new short-acting muscle relaxant, in anaesthetized cats and on isolated muscle preparations". Clinical and Experimental Pharmacology & Physiology. 2 (2): 159–170. doi:10.1111/j.1440-1681.1975.tb01830.x. PMID 237641. S2CID 21840628.
  12. ^ Page Module:Citation/CS1/styles.css has no content.Teerapong P, Marshall IG, Harvey AL, Singh H, Paul D, Bhardwaj TR, et al. (Aug 1979). "The effects of dihydrochandonium and other chandonium analogues on neuromuscular and autonomic transmission". The Journal of Pharmacy and Pharmacology. 31 (8): 521–528. doi:10.1111/j.2042-7158.1979.tb13576.x. PMID 39992. S2CID 37032460.
  13. ^ Page Module:Citation/CS1/styles.css has no content.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". Journal of the Chemical Society, Perkin Transactions 1: 305–307. doi:10.1039/P19790000305.
  14. ^ Page Module:Citation/CS1/styles.css has no content.Singh H, Bhardwaj TR, Paul D (1979). "Steroids and related studies. Part 48. A chandonium iodide analogue possessing an acetylcholine-like moiety". Journal of the Chemical Society, Perkin Transactions 1: 2451. doi:10.1039/p19790002451.
  15. ^ Page Module:Citation/CS1/styles.css has no content.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". The Journal of Pharmacy and Pharmacology. 33 (7): 451–457. doi:10.1111/j.2042-7158.1981.tb13831.x. PMID 6115032. S2CID 26115020.
  16. ^ Page Module:Citation/CS1/styles.css has no content.Jindal DP, Piplani P, Fajrak H, Prior C, Marshall IG (Feb 2001). "Synthesis and neuromuscular blocking activity of 16β-piperidinosteroidal derivatives". European Journal of Medicinal Chemistry. 36 (2): 195–202. doi:10.1016/s0223-5234(00)01205-8. PMID 11311750.
  17. ^ Page Module:Citation/CS1/styles.css has no content.Jindal DP, Piplani P, Fajrak H, Prior C, Marshall IG (Nov 2002). "Synthesis and neuromuscular blocking activity of 16β-N-methylpiperazino steroidal derivatives". European Journal of Medicinal Chemistry. 37 (11): 901–908. doi:10.1016/s0223-5234(02)01413-7. PMID 12446049.
  18. ^ Page Module:Citation/CS1/styles.css has no content.Singh H, Chaudhary AK (May 1985). "Pharmacokinetics and disposition of chandonium iodide in rat". Indian Journal of Experimental Biology. 23 (5): 253–257. PMID 4077122.
  19. ^ Page Module:Citation/CS1/styles.css has no content.Singh H, Chaudhary AK (May 1985). "Pharmacokinetics and disposition of chandonium iodide in monkey". Indian Journal of Experimental Biology. 23 (5): 258–261. PMID 4077123.

Lua error in package.lua at line 80: module 'Module:Navbox/configuration' not found. Template:Nicotinic acetylcholine receptor modulators

Retrieved from "https://cosmopedia.co/index.php?title=Candocuronium_iodide&oldid=8428506"