The
nerve agent soman, a powerful inhibitor of
acetylcholinesterase (AChE; EC 3.1.1.7), causes an array of toxic effects in the central nervous system. Adamantyl
tenocyclidine derivative
Tamorf (1-[2-(2-thienyl)-2-adamantyl]
morpholine), a compound with potential activity at the
N-methyl-D-aspartate (
NMDA) receptors and with neuroprotective properties, is effective against convulsions and brain lesions related to
soman poisoning. The objective of this study was to evaluate the antidotal potency of
Tamorf (2.5 mg kg(-1)), which was tested alone as a pretreatment or in combination with
atropine (10.0 mg kg(-1)) as a
therapy in rats poisoned with two different sub-lethal doses of
soman (1/4 and 1/2 of LD50). The effect of
Tamorf was compared with
carbamate physostigmine (0.1 mg kg(-1)). The study also determined the possible genotoxic effects of
Tamorf and
physostigmine, especially primary DNA damage in white blood cells, liver and brain tissue.
Tamorf administered 5 min before
poisoning stopped
soman-induced
seizures, was successful against sub-lethal doses of
soman and protected AChE activity in the brain (P = 0.0014, P = 0.0019), and in plasma (P = 0.0464, P = 0.0405). Compared with
Tamorf,
physostigmine was slightly effective in the elimination of
soman-induced
poisoning in rats. The pharmacological effect of
Tamorf and
atropine was less effective as
therapy, but did not increase
soman toxicity (P > 0.05 for all interactions). The results obtained indicate that
Tamorf and
physostigmine are not genotoxic to rats in the concentrations tested. Treatment with
Tamorf seems to be a good alternative for current pretreatment in
soman poisoning. Its antidotal mechanism is complex and is based on combined biochemical and receptor properties.