Evaluation of SCH 39166 as PET ligand for central D1 dopamine receptor binding and occupancy in man.

Abstract:

:SCH 39166 is the first selective D1-dopamine receptor antagonist developed for clinical trials in schizophrenia. SCH 39166 was evaluated as a radioligand for PET, labeled with 11C, and as a D1-dopamine receptor antagonist after single oral doses in healthy men. After intravenous injection of [11C]SCH 39166 distribution of radioactivity in brain grossly reflected D1-dopamine receptor density. The putamen to cerebellum ratio at equilibrium was low (1.54 +/- 0.18 SD), which makes [11C]SCH 39166 less suitable as a radioligand for applied PET studies. Saturability of specific binding was demonstrated after IV injection of [11C]SCH 39166 with low specific radioactivity. Stereospecificity of binding was examined using the stereoisomer [11C]SCH 39165. D1-Receptor occupancy was demonstrated with [11C]SCH 39166 2 h after administration of single oral doses of unlabeled SCH 39166 to each of three healthy subjects (25, 100 and 400 mg). There was a substantial reduction of specific [11C]SCH 39166 uptake in the putamen after all doses. Single oral doses of 100 mg induced approximately 70% D1-dopamine receptor occupancy in the basal ganglia, which should be sufficient to investigate the antipsychotic potential of D1-dopamine receptor antagonism in clinical studies.

journal_title

Psychopharmacology

authors

Karlsson P,Sedvall G,Halldin C,Swahn CG,Farde L

doi

10.1007/BF02246067

subject

Has Abstract

pub_date

1995-10-01 00:00:00

pages

300-8

issue

3

eissn

0033-3158

issn

1432-2072

journal_volume

121

pub_type

临床试验,杂志文章
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    更新日期:2012-02-01 00:00:00

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    pub_type: 临床试验,杂志文章

    doi:10.1007/s002130050409

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    更新日期:1997-10-01 00:00:00

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    pub_type: 临床试验,杂志文章

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    pub_type: 杂志文章

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  • The presence of 7-hydroxychlorpromazine in CSF of chloropromazine-treated patients.

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    pub_type: 杂志文章

    doi:10.1007/BF00432774

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    更新日期:1982-01-01 00:00:00

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    更新日期:1993-01-01 00:00:00

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    pub_type: 杂志文章,评审

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  • Alcohol consumption in free-feeding rats: procedural, genetic and pharmacokinetic factors.

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    pub_type: 杂志文章

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    更新日期:1987-01-01 00:00:00

  • Cocaine administration dose-dependently increases sexual desire and decreases condom use likelihood: The role of delay and probability discounting in connecting cocaine with HIV.

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