Alcuronium chloride

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).

Alcuronium chloride

Clinical data
AHFS/Drugs.com	International Drug Names
ATC code	M03AA01 (WHO)
Pharmacokinetic data
Metabolism	not metabolized
Excretion	70–90% unchanged in urine 1.3ml/kg/min t1/2 2–4 hours
Identifiers
IUPAC name 4,4'-Didemethyl-4,4'-di-propenyltoxiferin-1-dichloride
CAS Number	23214-96-2^N
PubChem CID	5311001
IUPHAR/BPS	341
ChemSpider	20118193^Y
UNII	490DW6501Y
ChEBI	CHEBI:31185^Y
CompTox Dashboard (EPA)	DTXSID0045414
ECHA InfoCard	100.035.648
Chemical and physical data
Formula	C44H50N4O2^+2
Molar mass	666.910 g·mol^−1
3D model (JSmol)	Interactive image
SMILES [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 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^Y Key:CPYGBGOXCJJJGC-GKLGUMFISA-L^Y
^NY (what is this?)  (verify)

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

• The International Pharmacopoeia

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.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. 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.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. S2CID 534003.
• 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.