Binding of the D3-preferring antipsychotic candidate F17464 to dopamine D3 and D2 receptors: a PET study in healthy subjects with [
Adult
Antipsychotic Agents
/ metabolism
Brain
/ drug effects
Carbon Radioisotopes
/ metabolism
Dopamine Agonists
/ metabolism
Dopamine Antagonists
/ metabolism
Healthy Volunteers
Humans
Male
Middle Aged
Positron-Emission Tomography
/ methods
Protein Binding
/ drug effects
Receptors, Dopamine D2
/ metabolism
Receptors, Dopamine D3
/ antagonists & inhibitors
Schizophrenia
/ drug therapy
Antipsychotic
D2 receptor
D3 receptor
F17464
PET scan
Schizophrenia
[11C]-(+)-PHNO
dopamine receptors
receptor occupancy
Journal
Psychopharmacology
ISSN: 1432-2072
Titre abrégé: Psychopharmacology (Berl)
Pays: Germany
ID NLM: 7608025
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
01
08
2019
accepted:
31
10
2019
pubmed:
28
11
2019
medline:
29
7
2020
entrez:
28
11
2019
Statut:
ppublish
Résumé
F17464, a dopamine D3 receptor antagonist with relatively high D3 selectivity (70 fold vs D2 in vitro), exhibits an antipsychotic profile in preclinical studies, and therapeutic efficacy was demonstrated in a randomized placebo-controlled clinical trial in patients with schizophrenia (Bitter et al. Neuropsychopharmacology 44(11):1917-1924, 2019). This open-label study in healthy male subjects aimed at characterizing F17464 binding to D3/D2 receptors and the time course of receptor occupancy using positron emission tomography (PET) imaging with a D3-preferring tracer, [ PET scans were performed at baseline and following a single 30 mg or 15 mg dose of F17464 (3 subjects/dose), and blood samples were collected for pharmacokinetic analysis. Receptor occupancy was calculated based upon reduction in binding potential of the tracer following F17464 administration. The relationship between plasma F17464 concentration and D3/D2 receptor occupancy was modeled and the plasma concentration corresponding to 50% receptor occupancy (EC Both doses of F17464 robustly blocked [ Overall, F17464 was strongly D3-selective in healthy volunteers, a unique profile for an antipsychotic candidate drug.
Identifiants
pubmed: 31773210
doi: 10.1007/s00213-019-05387-w
pii: 10.1007/s00213-019-05387-w
doi:
Substances chimiques
Antipsychotic Agents
0
Carbon Radioisotopes
0
Dopamine Agonists
0
Dopamine Antagonists
0
Receptors, Dopamine D2
0
Receptors, Dopamine D3
0
Types de publication
Clinical Trial, Phase I
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
519-527Subventions
Organisme : Institut de Recherche Pierre Fabre (FR)
ID : N/A
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