Atracurium besylate

Chemical Properties

Atracurium besylate is a white to yellow-white powder with slight hygroscopicity. It is soluble in water and very soluble in ethanol, acetonitrile and dichloromethane. It contains three isomers: cis-cis, cis-trans and trans-trans.

Uses

Atracurium besylate is a neuromuscular-blocking drug or skeletal muscle relaxant in the category ofnon-depolarizing neuromuscular-blocking drugs, used adjunctively in anesthesiato facilitate endotracheal intubation and to provide skeletal muscle relaxationduring surgery or mechanical ventilation.The drug atracurium besylate can be used most advantageously if muscle twitch response to peripheral nerve stimulation is monitored.

Definition

ChEBI: Atracurium besylate is the bisbenzenesulfonate salt of atracurium. It has a role as a nicotinic antagonist and a muscle relaxant. It is a quaternary ammonium salt and an organosulfonate salt. It contains an atracurium.

Hazard

Extremely toxic.

Pharmacokinetics

Atracurium besylate, a new non-depolarizing neuromuscular blocking agent, with short to intermediary duration of action and no significant cardiovascular effects. Not dependent on kidney function for elimination, it provides clinical advantages over other non-depolarizing, neuromuscular blocking agents. In vitro, in human plasma, the half-life of the drug was similar to that in buffer at the same pH being approximately 25 min (Hughes and Chappie, 1980).

Synthesis

Atracurium is 2,2-[1,5-pentanediylbis[oxy(3-oxo-3,1-propanediyl)]] bis [1-[(3,4-dimethoxyphenyl)methyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-2-methylisoquinolinium] dibenzene sulfonate (15.1.12). This compound is synthesized from bis-acrylic ester of 1,5-pentandiol (15.1.10), which is synthesized from acrylic acid chloride and 1, 5-pentandiol. Two molecules of a secondary amine, tetrahydropapaverine, are joined to the product in a Michael reaction, forming compound (15.1.11). Then both nitrogen atoms are methylated by methylbenzenesulfonate, giving atracurium (15.1.12).

Metabolism

Atracurium besylate is a nondepolarizing neuromuscular blocker in which the quaternary ammonium groups are located in two substituted tetrahydroisoquinoline rings separated by an aliphatic diester. It has a duration of action slightly longer than that of succinylcholine. Atracurium is not metabolized in the liver; rather, it undergoes hydrolysis of the ester functional groups that connect the two quaternary nitrogens. It also undergoes Hofmann elimination, a nonenzymatic, base-catalyzed decomposition, to yield laudanosine, which is inactive. T hus, termination of the effects of atracurium are independent of renal elimination. Because of this unusual metabolic profile, it is useful in patients with hepatic or renal disease.

Raw materials

Preparation Products