title: Review of the value of huperzine as pretreatment of organophosphate poisoning.
abstract: Today, organophosphate (OP) nerve agents are still considered as potential threats in both military or terrorism situations. OP agents are potent irreversible inhibitors of central and peripheral acetylcholinesterases. Pretreatment of OP poisoning relies on the subchronic administration of the reversible acetylcholinesterase (AChE) inhibitor pyridostigmine (PYR). Since PYR does not penetrate into the brain, it does not afford protection against seizures and subsequent neuropathology induced by an OP agent such as soman. Comparatively, huperzine (HUP) is a reversible AChE inhibitor that crosses the blood-brain barrier. HUP is presently approved for human use or is in course of clinical trials for the treatment of Alzheimer's disease or myasthenia gravis. HUP is also used as supplementary drug in the USA for correction of memory impairment. Besides, HUP has also been successfully tested for pretreatment of OP poisoning. This review summarizes the therapeutical value of HUP in this field. Moreover, the modes of action of HUP underlying its efficacy against OP agents are described. Efficacy appears mainly related to both the selectivity of HUP for red cell AChE which preserves scavenger capacity of plasma butyrylcholinesterases for OP agents and to the protection conferred by HUP on cerebral AChE. Finally, recent data, showing that HUP seems to be devoid of deleterious effects in healthy subjects, are also presented. Globally, this review reinforces the therapeutical value of HUP for the optimal pretreatment of OP poisoning.
authors.affiliation: Unité de Neuropharmacologie, CRSSA, La Tronche, France. guylallement@compuserve.com
authors.forename: Guy
authors.initials: G
authors.lastname: Lallement
authors.forename: Valérie
authors.initials: V
authors.lastname: Baille
authors.forename: Dominique
authors.initials: D
authors.lastname: Baubichon
authors.forename: Pierre
authors.initials: P
authors.lastname: Carpentier
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Collombet
authors.forename: Pierre
authors.initials: P
authors.lastname: Filliat
authors.forename: Annie
authors.initials: A
authors.lastname: Foquin
authors.forename: Elise
authors.initials: E
authors.lastname: Four
authors.forename: Catherine
authors.initials: C
authors.lastname: Masqueliez
authors.forename: Guy
authors.initials: G
authors.lastname: Testylier
authors.forename: Laura
authors.initials: L
authors.lastname: Tonduli
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dorandeu
mesh_terms: D000470:Alkaloids; D000818:Animals; D002619:Chemical Warfare Agents / Q000506:poisoning; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D062025:Organophosphate Poisoning; D012717:Sesquiterpenes / Q000627:therapeutic use*
chemical_list: D000470:Alkaloids; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D012717:Sesquiterpenes; C050426:huperzine A