Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.
Homer
PSD-95
antipsychotics
dopamine
glutamate
postsynaptic density
synaptopathy
treatment-resistant schizophrenia
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
21 Mar 2023
21 Mar 2023
Historique:
received:
30
01
2023
revised:
15
03
2023
accepted:
17
03
2023
medline:
30
3
2023
entrez:
29
3
2023
pubmed:
30
3
2023
Statut:
epublish
Résumé
Schizophrenia is a severe psychiatric illness affecting almost 25 million people worldwide and is conceptualized as a disorder of synaptic plasticity and brain connectivity. Antipsychotics are the primary pharmacological treatment after more than sixty years after their introduction in therapy. Two findings hold true for all presently available antipsychotics. First, all antipsychotics occupy the dopamine D2 receptor (D2R) as an antagonist or partial agonist, even if with different affinity; second, D2R occupancy is the necessary and probably the sufficient mechanism for antipsychotic effect despite the complexity of antipsychotics' receptor profile. D2R occupancy is followed by coincident or divergent intracellular mechanisms, implying the contribution of cAMP regulation, β-arrestin recruitment, and phospholipase A activation, to quote some of the mechanisms considered canonical. However, in recent years, novel mechanisms related to dopamine function beyond or together with D2R occupancy have emerged. Among these potentially non-canonical mechanisms, the role of Na
Identifiants
pubmed: 36983018
pii: ijms24065945
doi: 10.3390/ijms24065945
pmc: PMC10051989
pii:
doi:
Substances chimiques
Antipsychotic Agents
0
Dopamine
VTD58H1Z2X
beta-Arrestins
0
Types de publication
Systematic Review
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
A.d.B. has received unrestricted research support from Janssen, Lundbeck, and Otsuka and lecture honoraria for educational meeting from Chiesi, Lundbeck, Roche, Sunovion, Vitria, Recordati, Angelini and Takeda; he has served on advisory boards for Eli Lilly, Jansen, Lundbeck, Otsuka, Roche, Vitria, Chiesi, Recordati, Angelini, Takeda. No activity is related directly or indirectly to the present manuscript content. All the other authors declare no conflict of interest.
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