Dose dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: a study using positron emission tomography and 11C-raclopride.

Détails

ID Serval
serval:BIB_736015F3CD8C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Dose dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: a study using positron emission tomography and 11C-raclopride.
Périodique
Psychopharmacology
Auteur(s)
Bench C.J., Lammertsma A.A., Dolan R.J., Grasby P.M., Warrington S.J., Gunn K., Cuddigan M., Turton D.J., Osman S., Frackowiak R.S.
ISSN
0033-3158 (Print)
ISSN-L
0033-3158
Statut éditorial
Publié
Date de publication
1993
Volume
112
Numéro
2-3
Pages
308-314
Langue
anglais
Notes
Publication types: Clinical Trial ; Journal Article ; Randomized Controlled TrialPublication Status: ppublish
Résumé
Positron emission tomography (PET) and 11C-raclopride were used to measure the occupancy of central dopamine D2 receptors by a new neuroleptic, CP-88,059-1. In a double blind dose escalation study, seven healthy male subjects received a predose of between 2 mg and 60 mg CP-88,059-1, 5 h before PET scanning. One additional subject was assigned to placebo predose. Receptor occupancy was defined as the percentage reduction in binding potential compared with that seen in the subject predosed with placebo and with that seen in seven unmedicated normal volunteers previously studied. Binding of 11C-raclopride decreased in a dose dependent manner, and 85% dopamine D2 receptor occupancy was achieved with the highest dose of CP-88,059-1. The findings confirm that brain dopamine D2 receptors are blocked by CP-88,059-1 and suggest that an effective antipsychotic dose will be between 20 mg and 40 mg. The study high-lights the potential of positron emission tomography in the preclinical evaluation of new drugs.
Mots-clé
Adult, Brain/drug effects, Brain/metabolism, Cerebrovascular Circulation/drug effects, Dopamine Antagonists/pharmacokinetics, Dopamine Antagonists/pharmacology, Dose-Response Relationship, Drug, Humans, Image Processing, Computer-Assisted, Male, Neostriatum/drug effects, Neostriatum/metabolism, Piperazines/pharmacokinetics, Prolactin/blood, Raclopride, Receptors, Dopamine D2/drug effects, Salicylamides/pharmacokinetics, Spiro Compounds/pharmacokinetics, Thiazoles, Tomography, Emission-Computed
Pubmed
Web of science
Création de la notice
25/09/2011 15:53
Dernière modification de la notice
20/08/2019 14:31
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