Glutamate receptor antagonists for neuroleptic malignant syndrome and akinetic hyperthermic parkinsonian crisis.

Abstract

Schizophrenia and Parkinson's disease have been considered inversely related neuropsychiatric disorders since the former has been attributed to increased dopaminergic transmission while the latter is thought to result from loss of dopaminergic neurons. It is in line with this concept that the classical neuroleptic (anti-schizophrenic) drugs cause as a side effect a drug-induced type of Parkinsonism. Most etiopathogenetic models hold that the "neuroleptic malignant syndrome" may result from "over-therapy" of schizophrenia, causing too widespread a block of dopaminergic transmission. The same clinical condition can be triggered by rapid discontinuation of dopaminergic medication in Parkinson's disease. Further, neuroleptic malignant syndrome shares key clinical features such as extrapyramidal motor disturbances and hyperthermia with a severe form of clinical deterioration in Parkinson's disease patients, the akinetic Parkinsonian crisis. Both conditions, neuroleptic malignant syndrome and Parkinsonian crisis, are resistant to anticholinergic treatment but may well respond to drugs with N-methyl-D-aspartate (NMDA) antagonistic properties such as amantadine and memantine. We advocate the use of NMDA receptor antagonists in these medical emergencies and link their clinical efficacy to the common pathophysiological pathway of increased excitatory amino acid neurotransmitter activity in neuroleptic malignant syndrome, Parkinsonian crisis, and dopamine agonist withdrawal states.