Neostigmine Myopathy Is a Calcium Ion-Mediated Myopathy Initially Affecting the Motor End-plate

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Abstract
Morphological techniques were used to determine the acute and chronic effects of neostigmine on rat muscles. Transient calcium deposits, eliminated by prior treatment of sections with ethyleneglycol bis (aminoethylether) tetracetate (EGTA), were independent of fiber type and found at sites corresponding to neostigmine-induced focal lesions. The dimension and number of focal lesions and calcium deposits gradually decreased with chronic drug treatment. Size, shape, and density of the calcium deposits varied. Alterations in the motor nerve terminal, synaptic space, and junctional fold persisted even when banding patterns at the motor end plates were intact. Characteristic intermediate findings consisted of rod bodies and ribosomal clusters. Such clusters were frequently mingled with clumped sarcoplasmic reticulums, T-systems, or mitochondria. Despite continued administration of neostigmine, focal myopathic changes, other than in the synaptic region of the end plates, were reversible.