title: Choice of approaches in developing novel medical countermeasures for nerve agent poisoning.
abstract: During the establishment of a research branch, all relevant matters encountered will be of interest to study. After having acquired a body of basal knowledge, it becomes possible to derive ideas or hypotheses for further elaboration of information. The purpose of the present study was to show that therapies for nerve agent poisoning based on specific neuropharmacological approaches can have greater probability for being successful than treatment regimens based on fragmental research or serendipitous discoveries. By following the guidelines for research in experimental epilepsy, neuronal target areas for nerve agents have been identified through lesion studies, and critical receptors for pharmacological treatment have been specified through microinfusion studies of rats. Subsequent experimentations have shown that the results achieved from microinfusion studies are transferable to systemic administration. It is demonstrated that a treatment regimen developed through the novel approach is more efficacious than regimens derived from conventional research on countermeasures. A therapy consisting of HI-6, levetiracetam, and procyclidine that has been worked out along the new lines, exerts powerful anticonvulsant capacity and appears to have universal utility as a stand-alone therapy against soman intoxication in rats. It would be of great interest to examine whether the latter findings can be expanded to other animal species than rats and other classical nerve agents than soman.
authors.affiliation: Norwegian Defence Research Establishment (FFI), Protection and Societal Security Division, P.O. Box 25, NO-2027 Kjeller, Norway.
authors.forename: Trond
authors.initials: T
authors.lastname: Myhrer
authors.affiliation: Norwegian Defence Research Establishment (FFI), Protection and Societal Security Division, P.O. Box 25, NO-2027 Kjeller, Norway. Electronic address: pal.aas@ffi.no.
authors.forename: Pål
authors.initials: P
authors.lastname: Aas
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D000931:Antidotes / Q000008:administration & dosage / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology*; D018678:Cholinergic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D000077287:Levetiracetam; D062025:Organophosphate Poisoning; D010091:Oximes / Q000008:administration & dosage / Q000627:therapeutic use; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D011352:Procyclidine / Q000008:administration & dosage / Q000627:therapeutic use; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D000931:Antidotes; D018678:Cholinergic Agents; D010091:Oximes; D011726:Pyridinium Compounds; D000077287:Levetiracetam; D011352:Procyclidine; C022870:asoxime chloride; D010889:Piracetam
keywords: Lesion studies; Microinfusion studies; Nerve agents; Pharmacological receptors; Target areas