The Role of Nitric Oxide Synthase Inhibitors in Schizophrenia

Curr Med Chem. 2016;23(24):2692-2705. doi: 10.2174/0929867323666160812151054.

Abstract

Close to 1% of the world population suffer from schizophrenia. Current medications for this chronic mental disorder have greatly improved treatment over the last half century or more, but, the newer atypical antipsychotics have proven to be disappointing, and enormous challenges remain. The negative symptoms and cognitive dysfunction in schizophrenia which greatly affect overall morbidity call for better treatments. Nitric oxide (NO), an intra- and inter-cellular messenger in the brain, is involved in the pathogenesis of schizophrenia, so excessive NO production might contribute to the pathology. This implies that it might be useful to reduce nitrergic activity, so molecules aiming to decrease NO production such as NO synthase (NOS) inhibitors might be candidates. Here, I critically review advances in research on these emerging molecules which hold promise although a note of caution is required on account of their potential neurotoxicity and narrow therapeutic window.

Publication types

  • Review

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Disease Models, Animal
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Ketamine / pharmacology
  • Ketamine / therapeutic use
  • NG-Nitroarginine Methyl Ester / pharmacology
  • NG-Nitroarginine Methyl Ester / therapeutic use
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase / metabolism
  • Phencyclidine / pharmacology
  • Phencyclidine / therapeutic use
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism
  • Schizophrenia / pathology

Substances

  • Enzyme Inhibitors
  • Nitric Oxide
  • Ketamine
  • Nitric Oxide Synthase
  • Phencyclidine
  • NG-Nitroarginine Methyl Ester