Alcuronium chloride

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by Citation bot (talk | contribs) at 23:54, 6 November 2019 (Alter: pmid, issue, pages. Formatted dashes. | You can use this bot yourself. Report bugs here.| Activated by User:Ost316 | Category:CS1 maint: untitled periodical | via #UCB_Category). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Alcuronium chloride
Clinical data
AHFS/Drugs.comInternational Drug Names
ATC code
Pharmacokinetic data
Metabolismnot metabolized
Excretion70–90% unchanged in urine 1.3ml/kg/min t1/2 2–4 hours
Identifiers
  • 4,4'-Didemethyl-4,4'-di-propenyltoxiferin-1-dichloride
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEBI
CompTox Dashboard (EPA)
ECHA InfoCard100.035.648 Edit this at Wikidata
Chemical and physical data
FormulaC44H50N4O2+2
Molar mass666.894 g/mol g·mol−1
3D model (JSmol)
  • [Cl-].[Cl-].OC\C=C6\C[N@+]4(CC=C)CC[C@@]58c%11ccccc%11N7\C=C9\[C@H]1C[C@H]2[C@@]%10(CC[N@@+]2(CC=C)C\C1=C\CO)c3ccccc3N(/C=C(/[C@H]6C[C@H]45)[C@H]78)[C@@H]9%10
  • InChI=1S/C44H50N4O2.2ClH/c1-3-17-47-19-15-43-35-9-5-7-11-37(35)45-26-34-32-24-40-44(16-20-48(40,18-4-2)28-30(32)14-22-50)36-10-6-8-12-38(36)46(42(34)44)25-33(41(43)45)31(23-39(43)47)29(27-47)13-21-49;;/h3-14,25-26,31-32,39-42,49-50H,1-2,15-24,27-28H2;2*1H/q+2;;/p-2/b29-13-,30-14-,33-25-,34-26-;;/t31-,32-,39-,40-,41-,42-,43+,44+,47-,48-;;/m0../s1 checkY
  • Key:CPYGBGOXCJJJGC-GKLGUMFISA-L checkY
 ☒NcheckY (what is this?)  (verify)

Alcuronium chloride is a neuromuscular blocking (NMB) agent, alternatively referred to as a skeletal muscle relaxant. It is a semi-synthetic substance prepared from C-toxiferine I,[1] a bis-quaternary alkaloid obtained from Strychnos toxifera. C-toxiferine I itself has been tested for its pharmacological action and noted to be a very long acting neuromuscular blocking agent[2] For a formal definition of the durations of actions associated with NMB agents, see page for gantacurium. The replacement of both the N-methyl groups with N-allyl moieties yielded N,N-diallyl-bis-nortoxiferine, now recognized as alcuronium (and at one time marketed as the proprietary agent called Alloferin).

Inclusion of the allylic functions presented an enhanced potential area of biotransformation, and thus alcuronium is observed to have a much shorter duration of neuromuscular blocking action than its parent C-toxiferine I.[3] It also has a more rapid onset of action, and is ~1.5 times as potent as tubocurarine.[4] The pharmacological action of alcuronium is readily reversed by neostigmine, and it produced little histamine release.[5] The major disadvantage of alcuronium is that it elicits a vagolytic effect produced by a selective atropine-like blockade of cardiac muscarinic receptors.[4][6][7]

Effects

  • Cardiovascular system: histamine release and blockage of the sympathetic ganglia including adrenal medulla could cause hypotension
  • Respiratory: apnea due to phrenic blockage but bronchoconstriction can occur from the histamine release
  • Central nervous system: no effect on intraoccular pressure
  • Autonomic ganglion blockade can cause decrease in gut motility

Special points

  • Duration of action prolonged in states of low potassium, calcium and protein, also in states of high magnesium and acidosis.
  • Pharmaceutically incompatible with thiopentone
  • Infusion can cause fixed dilated pupils

See also

References

  1. ^ Foldes FF (1954). "The Mode of Action of Quaternary Ammonium Type Neuromuscular Blocking Agents". Br. J. Anaesth. 26 (6): 394–398. doi:10.1093/bja/26.6.394. PMID 13208908.
  2. ^ Waser PG (1950). Helv. Physiol. Pharmacol. Acta. 8 (3): 342–50. PMID 14793878.{{cite journal}}: CS1 maint: untitled periodical (link)
  3. ^ Martin-Smith M (1971), In: Ariens EJ (ed.), "Drug Design". Vol. 2. Academic Press. New York and London. pp.453-530.
  4. ^ a b Speight TM, Avery GS (1972). "Pancuronium Bromide: A Review of its Pharmacological Properties and Clinical Application". Drugs. 4 (3–4): 163–226. doi:10.2165/00003495-197204030-00002. PMID 4264763.
  5. ^ Thompson MA (1980). Br. J. Hosp. Med. 23 (2): 153–4, 163–4, 167-8 passim. PMID 6102875.{{cite journal}}: CS1 maint: untitled periodical (link)
  6. ^ Coleman AJ, Downing JW, Leary WP, Moyes DG, Styles M (1972). "The immediate cardiovascular effects of pancuronium, alcuronium and tubocurarine in man". Anaesthesia. 27 (4): 415–22. doi:10.1111/j.1365-2044.1972.tb08247.x. PMID 4264060.
  7. ^ Hughes R, Chapple DJ (1976). "Effects of Non-Depolarizing Neuromuscular Blocking Agents on Peripheral Autonomic Mechanisms in Cats". Br. J. Anaesth. 48 (2): 59–68. doi:10.1093/bja/48.2.59. PMID 130154.

Further reading

  • Zahn K, Eckstein N, Tränkle C, Sadée W, Mohr K (2002). "Allosteric modulation of muscarinic receptor signaling: alcuronium-induced conversion of pilocarpine from an agonist into an antagonist". J Pharmacol Exp Ther. 301 (2): 720–8. doi:10.1124/jpet.301.2.720. PMID 11961078.
  • Maass A, Mohr K (1996). "Opposite effects of alcuronium on agonist and on antagonist binding to muscarinic receptors". Eur J Pharmacol. 305 (1–3): 231–4. doi:10.1016/0014-2999(96)00240-3. PMID 8813558.
  • Jakubík J, Tucek S (1994). "Protection by alcuronium of muscarinic receptors against chemical inactivation and location of the allosteric binding site for alcuronium". J Neurochem. 63 (5): 1932–40. doi:10.1046/j.1471-4159.1994.63051932.x. PMID 7931349.
  • Proska J, Tucek S (1994). "Mechanisms of steric and cooperative actions of alcuronium on cardiac muscarinic acetylcholine receptors". Mol Pharmacol. 45 (4): 709–17. PMID 8183250.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Alcuronium_chloride&oldid=924960838"