Prevention of phospholine-induced myopathy with d-tubocurarine, atropine sulfate, diazepam, and creatine phosphate.
Acute administration of phospholine [diethyl-S-(2-dimethyl aminoethyl)phosphorothioate] at 0.2 mg/kg sc produces a myopathy characterized by initial focal changes in the subsynaptic area of the skeletal muscle. The onset of the myopathy is associated with fasciculations of high frequency. Agents that either prevent or reduce the fasciculations, such as d-tubocurarine, atropine sulfate, and diazepam, were effective in reducing the number of muscle lesions. These agents may reduce spontaneous muscle activity by blocking the postsynaptic receptor, by modifying the ionic-channel characteristics, by reducing presynaptic acetylcholine (ACh) release, or by a combination of any of these mechanisms. Creatine phosphate (CP) does not reduce fasciculations, but it is effective in reducing the number of necrotic fibers, probably by stimulating and sustaining the mechanism of Ca2+ uptake into the sarcoplasmic reticulum. It is postulated that an increase in the sarcoplasmic Ca2+ concentration triggers the events that lead to muscle necrosis.
D000818:Animals; D001285:Atropine / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects / Q000473:pathology; D003975:Diazepam / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008297:Male; D009132:Muscles / Q000187:drug effects*; D009135:Muscular Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D009946:Organothiophosphorus Compounds / Q000037:antagonists & inhibitors / Q000506:poisoning*; D010725:Phosphocreatine / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D014403:Tubocurarine / Q000627:therapeutic use*
D009946:Organothiophosphorus Compounds; D010725:Phosphocreatine; D001285:Atropine; C003415:amiton; D003975:Diazepam; D002118:Calcium; D014403:Tubocurarine