The main site of action of
diazepam, as with other
benzodiazepines, is at the
GABA(A) receptor, although it has been suggested that some of the potentially beneficial actions of
diazepam in
nerve agent poisoning are mediated through other means. It is likely that convulsions may have long-term sequelae in the central nervous system, because of damage by
anoxia and/or excitotoxicity. Numerous pharmacodynamic studies of the action of
diazepam in animals experimentally poisoned with
nerve agents have been undertaken. In nearly all of these,
diazepam has been studied in combination with other antidotes, such as
atropine and/or pyridinium
oximes, sometimes in combination with
pyridostigmine pretreatment. These studies show that
diazepam is an efficacious
anticonvulsant in
nerve agent poisoning. There is considerable experimental evidence to support the hypothesis that
diazepam (and other
anticonvulsants) may prevent structural damage to the central nervous system as evidenced by neuropathological changes such as neuronal
necrosis at autopsy. In instances of
nerve agent poisoning during terrorist use in Japan,
diazepam seems to have been an effective
anticonvulsant. Consequently, the use of
diazepam is an important part of the treatment regimen of
nerve agent poisoning, the aim being to prevent convulsions or reduce their duration.
Diazepam should be given to patients poisoned with
nerve agents whenever convulsions or muscle
fasciculation are present. In severe
poisoning,
diazepam administration should be considered even before these complications occur.
Diazepam is also useful as an
anxiolytic in those exposed to
nerve agents.