Abstract

The neuroleptic malignant syndrome (NMS) is an uncommon but serious adverse effect of antipsychotic medication. Similarities in the clinical picture, and muscle alterations, between NMS and susceptibility to malignant hyperthermia (MH) suggest common mechanisms underlying both disorders. Sarcoplasmic ionic calcium concentration ([Ca 2+] i) was measured by means of Ca 2+ selective microelectrodes in intact intercostal muscle fibers isolated from NMS patients and from subjects with no evidence of neuromuscular disease, who served as controls. The mean resting membrane potential and [Ca 2+] i were −84 ± 0.4 mV and 0.11 ± 0.01 μM (mean ± SEM) in the control subjects, while they were −84± 0.6 mV and 0.51 ± 0.02 μM in NMS muscle fibers. Only the difference in [Ca 2+] i is significant ( P <0.001). The incubation of control and NMS muscle bundles in dantrolene (10 −6M) induced a reduction of [Ca 2+] i to 0.06 ± 0.01 μM and 0.20 ± 0.04 μM respectively. These results shown an alteration in sarcoplasmic ionic [Ca 2+] in NMS muscle fibers, suggesting that a dysfunction in skeletal muscle plays some role in the pathogenesis of NMS.

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