PMID- 25296946
OWN - NLM
STAT- MEDLINE
DCOM- 20160118
LR  - 20161125
IS  - 1440-1819 (Electronic)
IS  - 1323-1316 (Linking)
VI  - 69
IP  - 5
DP  - 2015 May
TI  - Psychopharmacology of atypical antipsychotic drugs: From the receptor binding 
      profile to neuroprotection and neurogenesis.
PG  - 243-58
LID - 10.1111/pcn.12242 [doi]
AB  - 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-3beta (GSK-3beta). 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-3beta. Moreover, atypical APD increase brain-derived 
      neurotrophic factor (BDNF) levels. BDNF increases Ser9 phosphorylation of GSK-3beta 
      and has neuroprotective and neurogenic effects, as in the case of atypical APD. 
      These findings suggest that GSK-3beta might play a role in the action mechanisms of 
      atypical APD, in both the 5-HT-dependent and BDNF-dependent mechanisms.
CI  - (c) 2014 The Authors. Psychiatry and Clinical Neurosciences (c) 2014 Japanese Society 
      of Psychiatry and Neurology.
FAU - Kusumi, Ichiro
AU  - Kusumi I
AD  - Department of Psychiatry, Hokkaido University Graduate School of Medicine, 
      Sapporo, Japan.
FAU - Boku, Shuken
AU  - Boku S
FAU - Takahashi, Yoshito
AU  - Takahashi Y
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20141106
PL  - Australia
TA  - Psychiatry Clin Neurosci
JT  - Psychiatry and clinical neurosciences
JID - 9513551
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Receptors, Dopamine)
RN  - 0 (Receptors, Serotonin)
RN  - EC 2.7.11.1 (GSK3B protein, human)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Antipsychotic Agents/*pharmacology/*therapeutic use
MH  - Brain/drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Humans
MH  - Neurogenesis/*drug effects
MH  - Neuroprotection/*drug effects
MH  - Receptors, Dopamine/*metabolism
MH  - Receptors, Serotonin/*metabolism
OTO - NOTNLM
OT  - atypicality
OT  - brain-derived neurotrophic factor
OT  - dopamine
OT  - glycogen synthase kinase-3beta
OT  - serotonin
EDAT- 2014/10/10 06:00
MHDA- 2016/01/19 06:00
CRDT- 2014/10/10 06:00
PHST- 2014/10/06 00:00 [accepted]
PHST- 2014/10/10 06:00 [entrez]
PHST- 2014/10/10 06:00 [pubmed]
PHST- 2016/01/19 06:00 [medline]
AID - 10.1111/pcn.12242 [doi]
PST - ppublish
SO  - Psychiatry Clin Neurosci. 2015 May;69(5):243-58. doi: 10.1111/pcn.12242. Epub 
      2014 Nov 6.