World Library  
Flag as Inappropriate
Email this Article

Doxacurium chloride

Article Id: WHEBN0006139750
Reproduction Date:

Title: Doxacurium chloride  
Author: World Heritage Encyclopedia
Language: English
Subject: Muscle relaxants, Lorbamate, Styramate, Flopropione, Cyclarbamate
Collection:
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Doxacurium chloride

Doxacurium chloride
Systematic (IUPAC) name
bis[3-[6,7,8-trimethoxy-2-methyl-1- [(3,4,5-trimethoxyphenyl)methyl]- 3,4-dihydro-1H- isoquinolin-2-yl] propyl] butanedioate dichloride
Clinical data
Legal status
  • Worldwide: prescription only medicine
Routes of
administration
IV only
Pharmacokinetic data
Bioavailability 100% (IV)
Identifiers
CAS Registry Number  YesY
ATC code M03
PubChem CID:
DrugBank  YesY
ChemSpider  YesY
UNII  YesY
KEGG  YesY
ChEBI  YesY
ChEMBL  N
Chemical data
Formula C56H78Cl2N2O16
Molecular mass 1106.13 g/mol
 N   

Doxacurium chloride (formerly recognized as BW938U80 or BW A938U) is a neuromuscular-blocking drug or skeletal muscle relaxant in the category of non-depolarizing neuromuscular-blocking drugs, used adjunctively in anesthesia to provide skeletal muscle relaxation during surgery or mechanical ventilation. Unlike a number of other related skeletal muscle relaxants, it is rarely used adjunctively to facilitate endotracheal intubation.

Contents

  • Chemistry 1
  • Availability 2
  • History 3
  • References 4

Chemistry

Doxacurium is a symmetrical molecule because it is a diester of succinic acid.

The pharmacological action of doxacurium is a function of its competitive antagonism to acetylcholine receptors of the nicotinic type. The drug is marketed worldwide under the tradename of Nuromax, and it is classified as a long-duration non-depolarizing neuromuscular blocking agent in a class of compounds commonly and most erroneously referred to as "benzylisoquinolines" when, in fact, it is a bisbenzyltetrahydroisoquinolinium agent. The pharmaceutical preparation comprises the three trans-trans isomers (a meso structure R,S-S,R-doxacurium and an enantiomeric pair R,S-R,S-doxacurium and S,R-S,R-doxacurium)

Availability

Doxacurium is available worldwide although, for a number of years, its use has not been popular because of considerably long duration of action. Its decline from clinical use was even further hastened when the sister molecule, mivacurium chloride, was introduced into the clinic very shortly after doxacurium's debut. The only perceived advantange of doxacurium over that of mivacurium is its superior cardiovascular profile, with particular reference to the lack of histamine release when administered as a rapid bolus dose.

History

Doxacurium represents the second generation of tetrahydroisoquinolinium neuromuscular blocking drugs in a long lineage of nicotinic acetylcholine receptor antagonists synthesized by Mary M. Jackson and James C. Wisowaty, PhD (both chemists within the Chemical Development Laboratories at Burroughs Wellcome Co., Research Triangle Park, NC) in collaboration with John J. Savarese MD (who at the time was an anesthesiologist in the Dept. of Anesthesia, Harvard Medical School at the Massachusetts General Hospital, Boston, MA). Specifically, doxacurium was first synthesized in 1980. Early structure-activity studies had confirmed that the bulky nature of the "benzylisoquinolinium" entity provided a non-depolarizing mechanism of action. Partial saturation of the benzylisoquinoline ring to the tetrahydroisoquinoline ring provided an even further increase in potency of the molecules without detrimental effects to other pharmacological properties: this key finding led to the rapid adoption of the tetrahydroisoquinolinium structures as a standard building block (along with a 1-benzyl attachment), and it is the primary reason why the continued unwarranted reference to "benzylisoquinolinium" is a complete misnomer for all clinically introduced and currently used neuromuscular blocking agents in this class because they are all, in fact, tetrahydroisoquinoline derivatives. By definition, therefore, there has never been, in the history of clinical anesthetic practice, the use of a benzylisoquinoline neuromuscular blocking agent.

The heritages of doxacurium and mivacurium hark back to the synthesis of numerous compounds following structure-activity relationships that drove researchers to find the ideal replacement for succinylcholine (suxamethonium). Both doxacurium and mivacurium are descendants of early vigorous attempts to synthesize potent non-depolarizing agents with pharmacophoric elements derived from cross-combinations of the non-depolarizing agent, laudexium, and the well-known depolarizing agent, succinylcholine (suxamethonium). Ironically, laudexium itself was invented by a cross-combination between the prototypical non-depolarizing agent, d-tubocurarine and the depolarizing agent, decamethonium. In the 1950s and 1960s, the present-day concept of a neuromuscular blocking agent with a rapid onset and an ultra-short duration of action had not taken root: researchers and clinicians were still on the quest for potent but non-depolarizing replacements devoid of the histamine release and the dreaded "recurarizing" effects seen with tubocurarine and, more importantly, the absence of a depolarizing mechanism of action as seen with succinylcholine and decamethonium.

References

This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 


Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.