NMS may also be precipitated by the withdrawal of amantadine, levodopa, or other dopaminergic drugs used to treat Parkinson's disease.
NMS is primarily a disorder of excessive heat production.
It is probably precipitated by the blockade of dopaminergic receptors in the corpus striatum, leading to uncontrolled contractions of skeletal muscle, which, in turn, produce excessive body heat. NMS does not reflect either a genetic predisposition or drug overdose. Physical exhaustion, dehydration, and underlying organic brain syndrome have been cited as predisposing factors. Some patients who have recovered from NMS have subsequently received neuroleptic agents without suffering recurrences of NMS, but recurrent NMS does develop in 30 percent of patients who are rechallenged with neuroleptics. The clinical features of NMS evolve rapidly, usually over a period of one to three days.