Vasopressin V1B Receptor Antagonists as Potential Antidepressants.
ABT-436
SSR149415
TS-121
V1B receptor antagonist
hypothalamus-pituitary-adrenal axis
Journal
The international journal of neuropsychopharmacology
ISSN: 1469-5111
Titre abrégé: Int J Neuropsychopharmacol
Pays: England
ID NLM: 9815893
Informations de publication
Date de publication:
14 07 2021
14 07 2021
Historique:
received:
19
10
2020
revised:
04
03
2021
accepted:
16
03
2021
pubmed:
19
3
2021
medline:
1
2
2022
entrez:
18
3
2021
Statut:
ppublish
Résumé
Accumulating evidence shows that certain populations of depressed patients have impaired hypothalamus-pituitary-adrenal (HPA) axis function. Arginine-vasopressin (AVP) is one of the primary factors in HPA axis regulation under stress situations, and AVP and its receptor subtype (V1B receptor) play a pivotal role in HPA axis abnormalities observed in depression. Based on this hypothesis, several non-peptide V1B receptor antagonists have been synthesized, and the efficacies of some V1B receptor antagonists have been investigated in both animals and humans. V1B receptor antagonists exert antidepressant-like effects in several animal models at doses that attenuate the hyperactivity of the HPA axis, and some of their detailed mechanisms have been delineated. These results obtained in animal models were, at least partly, reproduced in clinical trials. At least 2 V1B receptor antagonists (TS-121 and ABT-436) showed tendencies to reduce the depression scores of patients with major depressive disorder at doses that attenuate HPA axis hyperactivity or block the pituitary V1B receptor. Importantly, TS-121 showed a clearer efficacy for patients with higher basal cortisol levels than for those with lower basal cortisol levels, which was consistent with the hypothesis that V1B receptor antagonists may be more effective for patients with HPA axis hyperactivity. Therefore, V1B receptor antagonists are promising approaches for the treatment of depression involving HPA axis impairment such as depression.
Identifiants
pubmed: 33733667
pii: 6176178
doi: 10.1093/ijnp/pyab013
pmc: PMC8278797
doi:
Substances chimiques
Antidepressive Agents
0
Antidiuretic Hormone Receptor Antagonists
0
Receptors, Vasopressin
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
450-463Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of CINP.
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