Discovery - University of Dundee - Online Publications

Library & Learning Centre

Receptor occupancy and brain free fraction

Receptor occupancy and brain free fraction

Research output: Contribution to journalArticle

View graph of relations

Authors

  • Jeanette Watson
  • Sara Wright
  • Adam Lucas
  • Kirsten L. Clarke
  • Jean Viggers
  • Sharon Cheetham
  • Phil Jeffrey
  • Rod Porter
  • Kevin D. Read (Lead / Corresponding author)

Research units

Info

Original languageEnglish
Pages753-760
Number of pages8
JournalDrug Metabolism and Disposition
Journal publication dateApr 2009
Journal number4
Volume37
DOIs
StatePublished

Abstract

This study was designed to investigate whether brain unbound concentration (C-u,C-brain) is a better predictor of dopamine D-2 receptor occupancy than total brain concentration, cerebrospinal fluid concentration (C-CSF), or blood unbound concentration (C-u,C-blood). The ex vivo D-2 receptor occupancy and concentration-time profiles in cerebrospinal fluid, blood, and brain of six marketed antipsychotic drugs were determined after oral administration in rats at a range of dose levels. The C-u,C-brain was estimated from the product of total brain concentration and unbound fraction, which was determined using a brain homogenate method. In conclusion, the C-u,C-brain of selected antipsychotic agents is a good predictor of D-2 receptor occupancy in rats. Furthermore, C-u,C-brain seems to provide a better prediction of D-2 receptor occupancy than C-CSF or C-u,C-blood for those compounds whose mechanism of entry into brain tissue is influenced by factors other than simple passive diffusion.

Documents

Library & Learning Centre

Contact | Accessibility | Policy