AMANTADINE AND THE GLUTAMATE HYPOTHESIS OF SCHIZOPHRENIA EXPERIENCES IN THE TREATMENT OF NEUROLEPTIC MALIGNANT SYNDROME

Amantadine was introduced for the pharmacological management of neurol eptic malignant syndrome (NMS) because of its beneficial effects in Pa rkinson's disease which were attributed to dopaminomimetic properties. While the dopaminomimetic effects of amantadine are weak under experi mental conditions, recent studies have confirmed that amantadine is an antagonist at the N-methyl-D-aspartate (NMDA) type of the glutamate r eceptor. Amantadine has psychotomimetic properties in patients with Pa rkinson's disease and normal controls. Two of four patients who receiv ed amantadine for NMS suffered an exacerbation of their psychiatric il lness. Our observations support the glutamate hypothesis of schizophre nia which suggests that reduced glutamatergic transmission causes a re lative dopaminergic excess in the basal ganglia and the limbic system.