Two primary hypotheses have been proposed to explain the pathophysiology
of the neuroleptic malignant syndrome (NMS): 1) that NMS is produced by
abrupt and extensive central dopamine receptor blockade by neuroleptics,
particularly in nigrostriatal and hypothalamic pathways; and 2) that NMS,
like malignant hyperthermia (MH), results from a preexisting defect in
skeletal muscle metabolism that is unmasked or provoked by neuroleptic
exposure. To evaluate these models, the authors review studies published
since 1980 of the clinical features, epidemiology, risk factors, laboratory
assessment, and relevant animal models of NMS and MH. Data from these
studies suggest that although NMS and MH are clinically similar, they are
pharmacologically distinct, implying that cross-reactivity between
triggering agents is unlikely to occur.Abstract Teaser