Comparative protective effects of HI-6 and MMB-4 against organophosphorous nerve agent poisoning.
Summary of "Comparative protective effects of HI-6 and MMB-4 against organophosphorous nerve agent poisoning."
The oximes pralidoxime (2-PAM), its dimethanesulphonate salt derivative P2S, and obidoxime (toxogonin) are currently licensed and fielded for the treatment of chemical warfare (CW) organophosphorous (OP) nerve agent poisoning. While they are effective against several of the identified threat CW OP agents, they have little efficacy against others such as soman (GD) and cyclosarin (CF). In addition, they are also significantly less effective than other investigational oximes against the nerve agent known as Russian VX (RVX). Among the oximes currently being investigated, two in particular, HI-6 (asoxime) and MMB-4 (ICD-039, methoxime) have been proposed as replacement therapies for the currently licensed oximes. HI-6 has been safely used in individuals to treat OP insecticide poisoning, as well as in human volunteers, although its efficacy against OP nerve agent poisoning in humans cannot be demonstrated due to ethical considerations. It is currently available for use in defined military settings in Canada, Sweden and the Czech Republic, and is also under development in a number of other countries. The oxime MMB-4 has not yet been studied clinically, but is fielded by the Czech Republic, and is being developed by the United States armed services as a replacement for the currently fielded 2-PAM. This review compares the effectiveness of HI-6 and MMB-4 against nerve agent threats where comparisons can be made. HI-6 has been demonstrated to be generally a superior reactivator of nerve agent inhibited enzyme, particularly with human and non-human primate derived enzyme, and has also shown better protective effects against the lethality of most OP agents in a variety of species. Both compounds appear to be clearly superior to the available oximes, obidoxime and 2-PAM.
Affiliation
Therapeutic Response Ltd., Medicine Hat, Alberta, Canada. PJlundy@shaw.ca
Journal Details
This article was published in the following journal.
Name: Toxicology
ISSN: 1879-3185
Pages: 90-6
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21524678
- DOI: http://dx.doi.org/10.1016/j.tox.2011.04.006
Medical and Biotech [MESH] Definitions
Ciguatera Poisoning
Poisoning caused by ingestion of SEAFOOD containing microgram levels of CIGUATOXINS. The poisoning is characterized by gastrointestinal, neurological and cardiovascular disturbances.
Shellfish Poisoning
Poisoning from toxins present in bivalve mollusks that have been ingested. Four distinct types of shellfish poisoning are recognized based on the toxin involved.
Saxitoxin
A compound that contains a reduced purine ring system but is not biosynthetically related to the purine alkaloids. It is a poison found in certain edible mollusks at certain times; elaborated by GONYAULAX and consumed by mollusks, fishes, etc. without ill effects. It is neurotoxic and causes RESPIRATORY PARALYSIS and other effects in MAMMALS, known as paralytic SHELLFISH poisoning.
Dimercaprol
An anti-gas warfare agent that is effective against Lewisite (dichloro(2-chlorovinyl)arsine) and formerly known as British Anti-Lewisite or BAL. It acts as a chelating agent and is used in the treatment of arsenic, gold, and other heavy metal poisoning.
Unithiol
A chelating agent used as an antidote to heavy metal poisoning.
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