The
nerve agent soman, as well as other
organophosphates such as
paraoxon and
phospholine in concentrations that caused
cholinergic symptoms induced a progressive dose-related
necrosis in rat skeletal muscle fibers. The severity of the
myopathy depended on a critical decrease in activity and duration of
acetylcholinesterase (AChE) inhibition. The number of muscle fibers affected was greatest with
soman, followed by tertiary
phospholine, paraxon , and quaternary
phospholine. The necrotic nerve fibers were repaired within 1 week.
Atropine and
gentamycin in concentrations that do not block neuromuscular transmission, attenuate the necrotic action of the
organophosphates by interacting with the presynaptic Ca2+ uptake mechanism. The half-time recovery rate of AChE after exposure to
soman varied between 12 hr for sciatic nerve, 5-9 days for muscle, and 14 days for brain. AChE activity of peripheral nerve was minimally inhibited by
soman and had recovered to control activity within 24 hr. The reason for this apparent insensitivity of the nerve AChE to
soman may be due to the high activity of an
enzyme that hydrolyzes
soman. AChE at the neuromuscular junction in part has a protective and regulatory function through its control of free
acetylcholine (ACh). By limiting the accumulation of ACh and the extent of its interaction with pre- and postsynaptic membranes, the morphological integrity of nerve terminals and muscle is preserved.