Anticonvulsant treatment of nerve agent seizures: anticholinergics versus diazepam in soman-intoxicated guinea pigs

Unequal Efficacy of Pyridinium Oximes in Acute Organophosphate Poisoning

“…The ultimate result is cessation of propagation of convulsions. 53 Diazepam is of benefit in organophosphate poisoned patients by reducing anxiety, restlessness and muscle fasciculations, terminating convulsions, and reducing morbidity and mortality when used in conjunction with atropine and oxime. Diazepam should be given to patients poisoned with OPCs whenever convulsions or pronounced muscle fasciculation are present.…”

A Guinea Pig Hippocampal Slice Model of Organophosphate-Induced Seizure Activity

“…In moderate-tosevere OP intoxication, a benzodiazepine (e.g., diazepam) may be added in an effort to control seizures and convulsions (Lallement et al, 1998;McDonough et al, 2000). However, benzodiazepine treatment, although efficacious in the majority of circumstances, has scope for improvement: OP-induced seizures can sometimes reoccur despite treatment, and even when seizures are abolished, neuronal damage can still arise (Hayward et al, 1990;Baze, 1993;.…”

Proceedings of the 2001 ECBC Scientific Conference on Chemical and Biological Defense Research, 6-8 March 2001, Marriott's Hunt Valley Inn, Hunt Valley, MD

“…Unlike previous results using rats 22 ' 26 , most of the tested anticholinergics were effective when given either shortly (5 min) or after a substantial delay (40 min) following seizure onset. However, the doses needed to achieve an anticonvulsant effect when treatment was delayed (40 min following seizure onset) were almost a log unit greater than those required of the same drugs when treatment was given shortly after exposure 29 . This indicated that there was a narrow therapeutic treatment window for producing an anticonvulsant effect with clinically relevant doses of anticholinergic drugs.…”

“…Initial structures for EFP calculations are obtained from an x-ray structure, MD simulations, many-body classical mechanics [23], or semi-empirical quantum chemistry. The effective fragment potential method was designed to model solvation effects [24][25][26][27][28][29][30] and is appropriately extended to describe protein interactions. The EFP are implemented in GAMESS [31] and have recently been applied to a variety of biomolecule problems [19][20][21][32][33][34][35][36][37].…”