title: Low dose morphine adjuvant therapy for enhanced efficacy of antipsychotic drug action: potential involvement of endogenous morphine in the pathophysiology of schizophrenia.
abstract: Major thematic threads linking extensive preclinical and clinical efforts have established a working mechanistic scheme whereby atypical antipsychotic drugs ameliorate negative DSM IV diagnostic criteria by effecting relatively potent blockade of serotonin (5-HT)(2A) receptors coupled with weaker antagonism of dopamine D(2) receptors in frontal cortical areas. These contentions are more or less supported by in vitro binding experiments employing cloned receptors on cultured cells, although significant functional involvement of 5-HT(2C) receptors has also been proposed. It is interesting that a key statistical analysis indicates a major shift in usage back to typical antipsychotic agents for management of schizophrenia from 1995-2008, whereas off-label usage of atypical antipsychotic agents was markedly increased or expanded for bipolar affective disorder. Importantly, meta-analyses generally did not support efficacy differences between the other atypical antipsychotics compared with the older typical agents. A critical examination of putative functional linkages of morphine and its type-selective mu opioid receptor to higher order cortical regulation of cognitive processes may provide novel insights into human behavioral processes that are severely impaired in schizophrenia spectrum disorders.
authors: Neuroscience Research Institute, State University of New York-College at Old Westbury, Old Westbury, NY 11568, USA. gstefano@sunynri.org
authors: George B
authors: GB
authors: Stefano
authors: Milena
authors: M
authors: Králíčková
authors: Radek
authors: R
authors: Ptacek
authors: Hana
authors: H
authors: Kuzelova
authors: Tobias
authors: T
authors: Esch
authors: Richard M
authors: RM
authors: Kream
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006801:Humans; D008954:Models, Biological; D009020:Morphine / Q000008:administration & dosage* / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D009020:Morphine