Premium
Combination anticonvulsant treatment of soman‐induced seizures
Author(s) -
Koplovitz I.,
Schulz S.,
Shutz M.,
Railer R.,
Macalalag R.,
Schons M.,
McDonough J.
Publication year - 2001
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.811
Subject(s) - soman , anticholinergic , pyridostigmine , diazepam , anticonvulsant , pharmacology , benzodiazepine , anesthesia , trihexyphenidyl , midazolam , convulsion , pyridostigmine bromide , medicine , atropine , parasympatholytic , chemistry , epilepsy , muscarinic acetylcholine receptor , acetylcholinesterase , sedation , biochemistry , myasthenia gravis , receptor , psychiatry , enzyme
Abstract These studies investigated the effectiveness of combination treatment with a benzodiazepine and an anticholinergic drug against soman‐induced seizures. The anticholinergic drugs considered were biperiden, scopolamine, trihexaphenidyl, and procyclidine; the benzodiazepines were diazepam and midazolam. Male guinea pigs were implanted surgically with cortical screw electrodes. Electrocorticograms were displayed continually and recorded on a computerized electroencephalographic system. Pyridostigmine (0·026 mg kg −1 , i.m.) was injected as a pretreatment to inhibit red blood cell acetylcholinesterase by 30–40%. Thirty minutes after pyridostigmine, 2 × LD 50 (56 µg kg −1 ) of soman was injected s.c., followed 1 min later by i.m. treatment with atropine (2 mg kg −1 ) + 2‐PAM (25 mg kg −1 ). Electrographic seizures occurred in all animals. Anticonvulsant treatment combinations were administered i.m. at 5 or 40 min after seizure onset. Treatment consisted of diazepam or midazolam plus one of the above‐mentioned anticholinergic drugs. All doses of the treatment compounds exhibited little or no antiseizure efficacy when given individually. The combination of a benzodiazepine and an anticholinergic drug was effective in terminating soman‐induced seizure, whether given 5 or 40 min after seizure onset. The results suggest a strong synergistic effect of combining benzodiazepines with centrally active anticholinergic drugs and support the concept of using an adjunct to supplement diazepam for the treatment of nerve‐agent‐induced seizures. Copyright © 2001 John Wiley & Sons, Ltd.