Effect of pyridostigmine on tetanic contracture of innervated and denervated rat skeletal muscle.
Pyridostigmine has been reported to cause histological damage and decrements in tetanic contracture of skeletal muscle. Cholinesterase inhibition, decreased transmitter release and desensitization of postsynaptic receptors have all been proposed as mechanisms for these effects. The purpose of the present study was to determine whether the effect of pyridostigmine to decrease tetanic contracture was due to pre- or postsynaptic action. Rats with innervated or chronically denervated hindlimbs were given pyridostigmine (25 mg/kg) s.c. by infusion for four days. Tetanic contracture (20, 50, 100 Hz) was evoked by sciatic nerve stimulation in the innervated muscles and direct muscle stimulation in the denervated muscles. Pyridostigmine significantly decreased the contracture of innervated triceps surae muscle in a frequency dependent manner. Post-tetanic potentiation was reduced from control muscle responses. In denervated muscle pyridostigmine had no effect on contracture or post-tetanic potentiation. These results show that innervation is required for the detrimental effect of pyridostigmine and that the drug has no effect on skeletal muscle.
Department of Pharmacology, Warner-Lambert/Parke-Davis, Pharmaceutical Research, Ann Arbor, Michigan.
R J
RJ
Anderson
D000818:Animals; D004558:Electric Stimulation; D001330:Electronic Data Processing; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009121:Muscle Denervation; D009132:Muscles / Q000294:innervation*; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011729:Pyridostigmine Bromide