Pyridostigmine-induced decrement in skeletal muscle contracture is not augmented by soman.
Previous studies have reported that pyridostigmine induces a decrement in contractile force generated during tetanic stimulation of skeletal muscle. Although our studies suggested that pyridostigmine affected release of transmitter from the motor nerve terminal, we could not exclude the possibility that the drug's action was due to depolarization blockade of the muscle brought on by excessive transmitter in the synaptic cleft. The purpose of this study was to determine whether the effect of combined treatment with pyridostigmine and an irreversible cholinesterase inhibitor (soman) would potentiate the decrement in muscle contracture observed with pyridostigmine alone. As reported previously, pyridostigmine (25 mg/kg) significantly reduced muscle contracture during tetanic stimulation (20-100 Hz), and soman (0.075 mg/kg) increased muscle contracture. Combined treatment with pyridostigmine and soman produced a decrease in muscle contracture equivalent to the effect of pyridostigmine alone. Since there was no evidence of depolarization blockade of the muscle despite aggressive treatment with two cholinesterase inhibitors, these results support the view that pyridostigmine has a significant presynaptic action to decrease neurotransmitter release. This action opposes the drug's inhibition of cholinesterase, and the net effect of combined treatment with pyridostigmine and soman is a muscle response which is largely unchanged from the effect of pyridostigmine alone.
Anderson
R J
RJ
Department of Pharmacology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Chamberlain
W L
WL
D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D002091:Butyrylcholinesterase / Q000097:blood; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000633:toxicity*
D012999:Soman; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D011729:Pyridostigmine Bromide