[New pharmacological approaches to the treatment of schizophrenia].
Schizophrenia is a serious mental disorder with a challenging rational pharmacotherapy. Neurochemical transmission in the dopaminergic system, especially via D2 receptors, and related changes in postsynaptic signal transduction are very important in both the formation of schizophrenia and current pharmacotherapeutic treatment with antipsychotic drugs. Blocking the serotonergic 5-HT2A and 5-HT2C receptors is growing growing importance with regard to the action mechanisms of new generation antipsychotic medications. Recent preclinical and clinical data show that dysfunction of central neurotrophins, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurophin-3 (NT-3) might contribute to impaired brain development and neuroplasticity, leading to schizophrenia. In addition, some recent studies suggest that there is an important relationship between alcohol and substance addiction, and schizophrenia. There is also some preclinical data indicating that the central nitrergic system and agmatine(3/4)a biologically active agent produced after decarboxylation of arginine(3/4)might be interesting and important targets for understanding the etiopathogenesis of schizophrenia and for development of new drugs. Selective dopamine D3 receptor antagonists, specific agonists for metabotropic and NMDA receptors of the glutamatergic system, and nicotinic alpha-7 receptor agonists were reported in preclinical and a limited number of clinical studies as potential new targets for schizophrenia treatment. In this review, new advances in the pharmacotherapy of schizophrenia and possible new targets are discussed in the light of the current literature.
Uzbay
I Tayfun
IT
Gülhane Askeri Tip Fak., Tibbi Farmakoloji AD., Ankara. tuzbay@gata.edu.tr
D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D006801:Humans; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D020933:Neurotrophin 3 / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000627:therapeutic use; D015398:Signal Transduction
D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D015259:Dopamine Agents; D020933:Neurotrophin 3; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D017448:Receptors, Dopamine D2; D012702:Serotonin Antagonists; D004298:Dopamine