Persistent binding at dopamine transporters determines sustained psychostimulant effects.
cathinones
dopamine transporter
drug-binding kinetics
new psychoactive substances
psychostimulants
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
07 02 2023
07 02 2023
Historique:
entrez:
2
2
2023
pubmed:
3
2
2023
medline:
7
2
2023
Statut:
ppublish
Résumé
Psychostimulants interacting with the dopamine transporter (DAT) can be used illicitly or for the treatment of specific neuropsychiatric disorders. However, they can also produce severe and persistent adverse events. Often, their pharmacological properties in vitro do not fully correlate to their pharmacological profile in vivo. Here, we investigated the pharmacological effects of enantiomers of pyrovalerone, α-pyrrolidinovalerophenone, and 3,4-methylenedioxypyrovalerone as compared to the traditional psychostimulants cocaine and methylphenidate, using a variety of in vitro, computational, and in vivo approaches. We found that in vitro drug-binding kinetics at DAT correlate with the time-course of in vivo psychostimulant action in mice. In particular, a slow dissociation (i.e., slow
Identifiants
pubmed: 36730201
doi: 10.1073/pnas.2114204120
pmc: PMC9963675
doi:
Substances chimiques
Dopamine Plasma Membrane Transport Proteins
0
Dopamine
VTD58H1Z2X
Central Nervous System Stimulants
0
Cocaine
I5Y540LHVR
Dopamine Uptake Inhibitors
0
Methylphenidate
207ZZ9QZ49
Banques de données
figshare
['10.6084/m9.figshare.14958270']
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2114204120Subventions
Organisme : Intramural NIH HHS
ID : Z01 DA000522
Pays : United States
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