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document
Dose-dependent effects of the CRF ( 1 ) receptor antagonist R317573 on regional brain activity in healthy male subjects . BACKGROUND Corticotropin-releasing factor receptor type 1 ( CRF ( 1 ) ) antagonists have been proposed as therapeutic agents in the treatment of mood and anxiety disorders although clinical evidence supporting their development and understanding of a dose-response relationship has been lacking . METHODS We tested two doses of the CRF ( 1 ) antagonist R317573 for effects on regional cerebral glucose metabolism ( rCMglu ) using [ ( 18 ) F ] fluoro-2-deoxy-D : -glucose ( FDG ) positron emission tomography ( PET ) following single-dose challenges in a double-blind , placebo-controlled , cross-over design , in 12 healthy male volunteers . RESULTS Single 30- and 200-mg doses of R317573 resulted in dose-related changes in rCMglu . Relative increases in rCMglu were observed in frontal cortical regions while relative decreases occurred in the putamen and right amygdala after both doses . Relative decreases occurred in cerebellum and right parahippocampal gyrus following the higher dose . CONCLUSIONS R317573 appears to produce acute dose-dependent changes in rCMglu . Effects occurred in regions that may be behaviorally relevant to mood and anxiety disorders . In some regions , these effects may be related to the receptor ( target ) density . Measuring acute effects on rCMglu with FDG-PET may offer a method for defining pharmacologically active doses for central nervous system targets for which selective radiotracers are lacking .
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Intervention_Pharmacological
CRF ( 1 ) receptor antagonist R317573
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Intervention_Pharmacological
Corticotropin-releasing factor receptor type 1 ( CRF ( 1 ) )
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Intervention_Pharmacological
CRF ( 1 ) antagonist R317573
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Intervention_Physical
fluoro-2-deoxy-D : -glucose ( FDG ) positron emission tomography ( PET )
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Intervention_Pharmacological
R317573
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Intervention_Pharmacological
R317573
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Intervention_Pharmacological
rCMglu
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Intervention_Physical
FDG-PET
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Outcome_Other
effects
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Outcome_Physical
regional cerebral glucose metabolism ( rCMglu
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Outcome_Physical
rCMglu
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Outcome_Physical
rCMglu
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Participant_Condition
healthy male subjects .
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Participant_Age
12 healthy male volunteers .