Sarin, a potent
cholinesterase inhibitor, induces an array of toxic effects including convulsions and behavioral impairments. We report here on the protection provided by post-exposure antidotal treatments against a lethal dose of
sarin (1.2xLD50) by
scopolamine,
benactyzine,
trihexyphenidyl or
caramiphen, administered 5, 10 or 20 min after the initiation of convulsions. A mixture of the
oxime TMB4 and
atropine (TA) was injected 1 min following
poisoning a paradigm that may represent a scenario reminiscent of a terror incident. Surviving TA-treated rats exhibited marked
tonic-clonic convulsions,
weight loss, poor clinical status and abnormal cognitive performance as assessed by the Morris water maze. Additionally, a dramatic increase in the density of peripheral
benzodiazepine receptors (PBRs), a faithful marker for neuronal damage, was noted. Animals treated 5 min after the development of toxic signs with
benactyzine,
trihexyphenidyl or
caramiphen demonstrated control levels of PBR values, whereas
scopolamine produced binding densities significantly above basal levels. Examined at the 10-min time point,
scopolamine and
trihexyphenidyl afforded no protection against brain damage and did not differ from TA-injected rats. All four drugs failed to significantly prevent the alterations when applied 20 min after onset of convulsions. Assessment of learning processes yielded similar results, where
caramiphen exibited some protection at the 20-min time point. Our results show that
caramiphen and
benactyzine, agents with combined
anticholinergic and antiglutamatergic pharmacological profiles, offer considerable shielding against
sarin, even when their administration is delayed.