Combination anticonvulsant treatment of soman-induced seizures

✍ Scribed by I. Koplovitz; S. Schulz; M. Shutz; R. Railer; R. Macalalag; M. Schons; J. McDonough

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 63 KB
• Volume: 21
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.811

✦ Synopsis

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 ) Y 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. Published in 2001 by John Wiley & Sons, Ltd.