Pitsikas Nikolaos
Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Thessaly, Panepistimiou 3 (Biopolis), 415-00 Larissa, Greece.
Curr Med Chem. 2016;23(24):2692-2705. doi: 10.2174/0929867323666160812151054.
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.
近1%的世界人口患有精神分裂症。在过去半个多世纪甚至更长时间里，针对这种慢性精神障碍的现有药物已极大地改善了治疗效果，然而，事实证明新型非典型抗精神病药物令人失望，且仍面临巨大挑战。精神分裂症中的阴性症状和认知功能障碍极大地影响了总体发病率，因此需要更好的治疗方法。一氧化氮（NO）作为大脑内和细胞间的信使，参与了精神分裂症的发病机制，所以过量的NO生成可能促使了病理过程的发生。这意味着降低一氧化氮能活性可能是有用的，因此旨在减少NO生成的分子如一氧化氮合酶（NOS）抑制剂可能是候选药物。在此，我审慎地回顾了这些新兴分子的研究进展，尽管鉴于它们潜在的神经毒性和狭窄的治疗窗需要谨慎对待，但它们仍颇具前景。
