Calcium channel blocker reverses anticholinesterase-induced myopathy.
Inhibition of the enzyme, acetylcholinesterase (AChE), at the neuromuscular junction by pyridostigmine (PYR) results in breakdown of the postjunctional folds and dissolution of the Z-discs. It is hypothesized that excess activation of the acetylcholine (ACh) receptors by unhydrolyzed ACh results in a large influx of calcium ions. This could possibly lead to the activation of calcium-dependent proteases, resulting in the observed myopathy. Pretreatment with the calcium channel blocker, diltiazem, followed by administration of both PYR and the calcium blocker resulted in a significant reduction in the extent of muscle damage due to PYR alone. In order to ascertain whether the calcium blocker could reverse the myopathy previously induced by PYR, the AChE inhibitor was administered first, resulting in significant muscle damage, followed the next day by diltiazem. After 7 days of diltiazem treatment, with continued administration of PYR, the calcium blocker significantly reduced the myopathy at the neuromuscular junction. The results are discussed in terms of possible clinical application of diltiazem in neuromuscular diseases (i.e. muscular dystrophy).
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Laboratory Service, Veterans Administration Medical Center, Portland, OR 97201.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D005260:Female; D009132:Muscles / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D002800:Cholinesterase Inhibitors; D004110:Diltiazem; D011729:Pyridostigmine Bromide