Psychopharmacology of atypical antipsychotic drugs: From the receptor binding profile to neuroprotection and neurogenesis
- 6 November 2014
- journal article
- review article
- Published by Wiley in Psychiatry and Clinical Neurosciences
- Vol. 69 (5), 243-258
- https://doi.org/10.1111/pcn.12242
Abstract
The original definition of atypical antipsychotic drugs (APD) was drugs that are effective against positive symptoms in schizophrenia with no or little extrapyramidal symptoms (EPS). However, atypical APD have been reported to be more effective for cognitive dysfunction and negative symptoms in schizophrenia than typical APD, which expands the definition of 'atypicality'. This article provides a critical review of the pharmacology of atypical APD, especially from the viewpoint of receptor binding profiles and neurotransmitter regulations as well as neuroprotection and neurogenesis. A variety of serotonin (5-HT) receptors, such as 5-HT2A / 2C , 5-HT1A , 5-HT6 and 5-HT7 receptors, may contribute to the mechanisms of action of 'atypicality'. The dopaminergic modulations, including a low affinity for dopamine D2 receptors and a partial D2 receptor agonistic action, and glutamatergic regulations may also be involved in the pharmacological backgrounds of 'atypicality'. Atypical APD, but not typical APD, may facilitate cortical neuroprotection and hippocampal neurogenesis, which might be a part of the action mechanisms of atypical APD. The facilitation of cortical neuroprotection and hippocampal neurogenesis induced by atypical APD might be mediated by an increase in the Ser9 phosphorylation of glycogen synthase kinase-3β (GSK-3β). The stimulation of 5-HT1A receptors and/or the blockade of 5-HT2 receptors, which is characteristic of atypical APD, might increase Ser9 phosphorylation of GSK-3β. Moreover, atypical APD increase brain-derived neurotrophic factor (BDNF) levels. BDNF increases Ser9 phosphorylation of GSK-3β and has neuroprotective and neurogenic effects, as in the case of atypical APD. These findings suggest that GSK-3β might play a role in the action mechanisms of atypical APD, in both the 5-HT-dependent and BDNF-dependent mechanisms.Keywords
This publication has 103 references indexed in Scilit:
- Functional significance of glycogen synthase kinase-3 regulation by serotoninCellular Signalling, 2012
- Noradrenaline increases neural precursor cells derived from adult rat dentate gyrus through beta2 receptorProgress in Neuro-Psychopharmacology and Biological Psychiatry, 2012
- Glycogen synthase kinase 3β inhibitors protect hippocampal neurons from radiation-induced apoptosis by regulating MDM2-p53 pathwayCell Death & Differentiation, 2011
- Serotonergic modulation of extrapyramidal motor disorders in mice and rats: Role of striatal 5-HT3 and 5-HT6 receptorsNeuropharmacology, 2011
- Implications of animal object memory research for human amnesiaNeuropsychologia, 2010
- Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivoPsychopharmacology, 2009
- Olanzapine and risperidone block a high dose of methamphetamine-induced schizophrenia-like behavioral abnormalities and accompanied apoptosis in the medial prefrontal cortexSchizophrenia Research, 2008
- Adult treatment with methamphetamine transiently decreases dentate granule cell proliferation in the gerbil hippocampusJournal of Neural Transmission, 2000
- In vivo occupation of dopamine D 1 , D 2 and serotonin 2A receptors by novel antipsychotic drug, SM-9018and its metabolite, in rat brainJournal of Neural Transmission, 1998
- Antagonism by 8-OH-DPAT, but not ritanserin, of catalepsy induced by SCH 23390 in the ratJournal of Neural Transmission, 1992