Amantadine and the glutamate hypothesis of schizophrenia. Experiences in the treatment of neuroleptic malignant syndrome

J Neural Transm Gen Sect. 1993;92(1):57-65. doi: 10.1007/BF01245162.


Amantadine was introduced for the pharmacological management of neuroleptic malignant syndrome (NMS) because of its beneficial effects in Parkinson's disease which were attributed to dopaminomimetic properties. While the dopaminomimetic effects of amantadine are weak under experimental conditions, recent studies have confirmed that amantadine is an antagonist at the N-methyl-D-aspartate (NMDA) type of the glutamate receptor. Amantadine has psychotomimetic properties in patients with Parkinson's disease and normal controls. Two of four patients who received amantadine for NMS suffered an exacerbation of their psychiatric illness. Our observations support the glutamate hypothesis of schizophrenia which suggests that reduced glutamatergic transmission causes a relative dopaminergic excess in the basal ganglia and the limbic system.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Amantadine / adverse effects*
  • Amantadine / therapeutic use
  • Antipsychotic Agents / adverse effects
  • Depressive Disorder / drug therapy
  • Depressive Disorder / psychology
  • Female
  • Glutamates / physiology*
  • Glutamic Acid
  • Humans
  • Male
  • Middle Aged
  • Neuroleptic Malignant Syndrome / drug therapy*
  • Schizophrenia / chemically induced*
  • Schizophrenia / complications
  • Schizophrenic Psychology


  • Antipsychotic Agents
  • Glutamates
  • Glutamic Acid
  • Amantadine