Savoxepine: striatal dopamine-D2 receptor occupancy in human volunteers measured using positron emission tomography (PET)

K. L. Leenders, A. Antonini, R. Thomann, J. T. Locher, L. Maître, A. Gerebtzoff, H. F. Beer, S. Ametamey, R. Weinreich, A. Gut, F. Gnirss, S. Ofner, W. Schilling, P. C. Waldmeier

Research output: Contribution to journalArticlepeer-review

Abstract

The extent and duration of striatal dopamine-D2 receptor occupancy by savoxepine in humans has been studied using positron emission tomography with [11C]-raclopride, in order to investigate why the anticipated favourable ratio between its extrapyramidal and antipsychotic effects was not achieved in practice. After 0.25 mg savoxepine, striatal D2 receptor occupancy peaked at 50-60% after 24-36 h and disappeared within 6 days. After doses of 0.1 mg to 0.5 mg, D2 receptor occupancy in the putamen and caudate nucleus increased from 20 to 70% 3-7 h after administration and amounted to 40 to 75% at the peak time (20-29 h). This suggests that cumulative D2 receptor blockade would occur if equal or increasing doses of savoxepine were given repeatedly. Extrapyramidal adverse-effects would be likely to occur under such circumstances. An adequate test of the theory that preference for hippocampal dopamine D2 receptors with afford a good therapeutic ratio requires an alternative dosing regimen.

Original languageEnglish
Pages (from-to)135-140
Number of pages6
JournalEuropean Journal of Clinical Pharmacology
Volume44
Issue number2
DOIs
Publication statusPublished - Mar 1993

Keywords

  • dopamine D receptor antagonist
  • healthy volunteers
  • Neuroleptic drug
  • positron emission tomography
  • Savoxepine
  • striatal receptor binding

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

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