Review of the value of gacyclidine (GK-11) as adjuvant medication to conventional treatments of organophosphate poisoning: Primate experiments mimicking various scenarios of military or terrorist attack by soman

Today, organophosphorus nerve agents are still considered as potential thre ats in both military or terrorism situations. These agents act as potent ir reversible inhibitors of acetylcholinesterase in both central and periphera l nervous systems. Conventional treatment of organophosphate poisoning incl udes the combined administration of a cholinesterase reactivator (an oxime) , a muscarinic cholinergic receptor antagonist (atropine) and a benzodiazep ine anticonvulsant (diazepam). However, numerous studies have demonstrated that the excitatory amino acid glutamate also plays a prominent role in the maintenance of organophosphate-induced seizures and in the subsequent neur opathology especially through an overactivation of the N-methyl-D-aspartate (NMDA) receptor subtype. Contrary to other non-competitive NMDA antagonist s successfully tested in rodents exposed to organophosphate, gacyclidine is a novel antiNMDA compound which is in the process of approval for human us e in France for neurotraumatology. This review summarizes the therapeutic v alue of gacyclidine as a complement to the available emergency treatment ag ainst severe organophosphate poisoning. Previous data obtained from experim ents on primates in several scenarios mimicking military or terrorist attac ks, using soman as the nerve agent, were used. Primates pretreated with pyr idostigmine and receiving conventional emergency therapy at the first signs of poisoning survive. However, only gacyclidine is able to ensure complete management of nerve agent poisoning for rapid normalization of EEG activit y, clinical recovery and neuroprotection. Gacyclidine also ensures optimal management of severe nerve agent poisoning in animals neither pretreated no r receiving emergency; therapy likewise during an unexpected exposure. Howe ver, this beneficial effect is obtained provided that medical intervention is conducted rapidly after intoxication. Globally, the current lack of any other NMDA receptor antagonist suitable for human use reinforces the therap eutic value of gacyclidine as a central nervous system protective agent for the treatment of OP poisoning. (C)1999 Intox Press, Inc.