Neuronal structures involved in the induction and propagation of seizures caused by nerve agents: implications for medical treatment.
In epilepsy research, studies have been made to identify brain areas critical for triggering and/or controlling propagated seizure activity. The purpose of the present study was to focus on a similar approach in nerve agent research by reviewing relevant literature to map potential trigger sites and propagation pathways for seizures. The piriform cortex and medial septal area emerge as prime target areas for soman-induced seizures. The cholinergic hyperactivation in the latter structures seems to induce increased glutamatergic activity in the piriform, entorhinal, and perirhinal cortices along with the hippocampal region. For prophylactic or early treatment, mapping of muscarinic subreceptors in the piriform cortex and medial septum would be guiding for designing anticholinergic drugs with optimal properties. Sustained seizures governed by glutamatergic over-activity may primarily be terminated by drugs with optimal glutamatergic antagonism primarily in the piriform, entorhinal, and perirhinal cortices. Studies of radiolabeled ligands to map subreceptors may provide specification of wanted drug properties to guide the choice among existing agents or to synthesize novel ones.
Myhrer
Trond
T
Norwegian Defence Research Establishment, Protection Division, NO-2027, Kjeller, Norway. trond.myhrer@ffi.no
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D051337:Chemical Terrorism; D002619:Chemical Warfare Agents / Q000633:toxicity*; D015195:Drug Design; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D019580:Perforant Pathway / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D012999:Soman / Q000633:toxicity*; D014857:Warfare
D002619:Chemical Warfare Agents; D012999:Soman