Neuroleptic malignant syndrome (NMS) was first recognized as a life-threatening 
complication of dopamine receptor antagonists characterized by extrapyramidal 
disturbances, hyperthermia, and elevated serum creatine kinase levels. Concepts 
of NMS have changed because medications other than classic neuroleptic drugs 
have been implicated as triggering agents and because syndromes identical to NMS 
have been observed in patients with Parkinson's disease withdrawn from their 
medication or suffering akinetic hyperthermic parkinsonian crisis. The 
neurochemical key features in all these conditions are probably functional 
dopamine deficiency and ensuing hyperactivity of excitatory amino acid 
neurotransmission in the basal ganglia and hypothalamus. Recognition of NMS is 
the most important step in its management; the outcome is good if causative 
drugs are discontinued or if parkinsonian therapy is readjusted. Supportive care 
includes management of hyperthermia and fluid replacement. Controversial 
therapeutic measures include the application of dopamine receptor agonists, 
excitatory amino acid antagonists, or dantrolene. Psychiatric patients with a 
history of NMS and psychotic relapse necessitating neuroleptic drugs do not 
commonly redevelop NMS when reexposed to dopamine receptor antagonists but may 
be treated most safely with atypical neuroleptic drugs such as clozapine.