W-84 dibromide

Names

[ Name ]:
W-84 dibromide

[Synonym ]:
Hexamethylene-bis-[dimethyl-(3-phthalimidopropyl)ammonium]dibromide
Hdmppa
W-84 dibromide
W-84

Biological Activity

[Description]:

W-84 (dibromide) is a potent allosteric modulator of M2-cholinoceptors, which retards [3H]N-methylscopolamine dissociation. W-84 dibromide can stabilize cholinergic antagonist-receptor complexes. W-84 (dibromide) is a non-competitive muscarinic acetylcholine receptors antagonist with allosteric effects. W-84 (dibromide) protects over additively against an organophosphate-intoxication when applied in combination with atropine[1][2][3].

[Related Catalog]:

Signaling Pathways >> Neuronal Signaling >> mAChR

Research Areas >> Others

Signaling Pathways >> GPCR/G Protein >> mAChR

[Target]

muscarinic acetylcholine receptors[1]

[In Vitro]

The stabilizing effect of W-84 (dibromide) on antagonist-receptor complexes may explain the overadditive protective action exerted by the combination of atropine and W-84 (dibromide) against organophosphate intoxication[1]. W-84 (dibromide) not only inhibits radioligand association but also strongly stabilizes antagonist-receptor complexes[2].

[References]

[1]. Jepsen K, et al. Allosteric stabilization of 3H-N-methylscopolamine binding in guinea-pig myocardium by an antidote against organophosphate intoxication. Pharmacol Toxicol. 1988;63(3):163-168.

[2]. Mohr K, et al. Equipotent allosteric effect of W84 on [3H]NMS-binding to cardiac muscarinic receptors from guinea-pig, rat, and pig. Pharmacol Toxicol. 1992;70(3):198-200.

[3]. Grossmüller M, et al. Allosteric site in M2 acetylcholine receptors: evidence for a major conformational change upon binding of an orthosteric agonist instead of an antagonist. Naunyn Schmiedebergs Arch Pharmacol. 2006;372(4):267-276.

Chemical & Physical Properties

[ Molecular Formula ]:
C₃₂H₄₄Br₂N₄O₄

[ Molecular Weight ]:
708.52400

[ Exact Mass ]:
706.17300

[ PSA ]:
74.76000

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Potentiation by alcuronium of the antimuscarinic effect of N-methylscopolamine in guinea pig left atria.

Eur. J. Pharmacol. 272 , 103-106, (1995)

Alcuronium is known to stabilize allosterically the binding of the muscarinic antagonist N-methylscopolamine to muscarinic M2 receptors and thus to elevate the equilibrium binding of N-methylscopolami...

Allosteric modulation of G protein-coupled receptors: perspectives and recent developments.

Drug Discov. Today 9 , 752-758, (2004)

Allosteric modulation of G protein-coupled receptors has recently been recognized as an alternative approach to gain selectivity in drug action. In this overview, allosteric modulators that enhance or...

A stable and highly potent hexamethonium derivative which modulates muscarinic receptors allosterically in guinea-pig hearts.

J. Pharm. Pharmacol. 46(2) , 108-12, (1994)

W84 (N,N,N',N'-tetramethyl-N,N'-bis-(3-phthalimidopropyl)-N,N'-hexane- 1,6- diyl-bis-ammonium dibromide) is a potent stabilizer of antagonist binding to muscarinic receptors; however, W84 hydrolyses i...