Flunarizine: a possible adjuvant medication against soman poisoning?
Organophosphate (OP) nerve agents are amongst the most toxic chemicals. One of them, soman, can induce severe epileptic seizures and brain damage for which therapy is incomplete. The present study shows that pretreatment with flunarizine (Flu), a voltage-dependent calcium channel blocker, when used alone, does not produce any beneficial effect against the convulsions, neuropathology and lethality induced by soman. Flu was also tested in combination with atropine sulfate and diazepam. In this case, although only some results reach statistical significance, an encouraging general trend toward an improvement of the anticonvulsant, neuroprotective and antilethal capacities of this classical anti-OP two-drug regimen is constantly observed. In the light of these findings, it seems premature to definitely reject (or recommend) Flu as a possible adjuvant medication against soman poisoning. Further studies are required to determine its real potential interest.
Centre de Recherches du Service de Santé des Armées, Unité de Neuropharmacologie, La Tronche Cedex, France. pierrecarpentier@crssa.net
Pierre
P
Carpentier
Annie
A
Foquin
Guy
G
Lallement
Fréderic
F
Dorandeu
D000818:Animals; D001285:Atropine / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002619:Chemical Warfare Agents / Q000633:toxicity*; D003975:Diazepam / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005444:Flunarizine / Q000627:therapeutic use*; D018757:GABA Modulators / Q000627:therapeutic use; D007928:Lethal Dose 50; D008297:Male; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D012999:Soman / Q000037:antagonists & inhibitors / Q000633:toxicity*
D002121:Calcium Channel Blockers; D002619:Chemical Warfare Agents; D018757:GABA Modulators; D018727:Muscarinic Antagonists; D001285:Atropine; D012999:Soman; D003975:Diazepam; D005444:Flunarizine