Psychopharmacology

, Volume 119, Issue 1, pp 1–8

Oral administration of NNC 756 — a placebo controlled PET study of D1-dopamine receptor occupancy and pharmacodynamics in man

  • P. Karlsson
  • L. Farde
  • C. Halldin
  • G. Sedvall
  • L. Ynddal
  • M. Sloth-Nielsen
Original Investigation

DOI: 10.1007/BF02246046

Cite this article as:
Karlsson, P., Farde, L., Halldin, C. et al. Psychopharmacology (1995) 119: 1. doi:10.1007/BF02246046

Abstract

NNC 756 is a new benzazepine with high affinity and selectivity for D1-dopamine receptors. In a double-blind, placebo controlled, cross-over study, positron emission tomography and the radioligand [11C]SCH 23390 were used to determine central D1-do-pamine receptor occupancy after a single oral dose of 80 mg NNC 756 in three healthy men. NNC 756 induced 75, 66 and 47% occupancy of D1-dopamine receptors in the putamen of at 1.5 h after drug administration and 46, 36 and 24% after 7.5 h. There was a hyperbolic relationship between the occupancy values and the serum concentrations. The Ki value for the hyperbola was 6.4 ng/ml (±SD 1.4). The occupancy at 1.5 h is on the same level as that shown to induce effects in animal models for prediction of antipsychotic effect. Restlessness (akathisia) appeared in two subjects and nausea in one subject at time of peak drug concentration in serum. The oral dose level of 80 mg should be appropriate to investigate the potential antipsychotic effect of NNC 756.

Key words

D1-dopamine receptors Positron emission tomography SCH 23390 NNC 756 Akathisia Nausea 

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • P. Karlsson
    • 1
  • L. Farde
    • 1
  • C. Halldin
    • 1
  • G. Sedvall
    • 1
  • L. Ynddal
    • 2
  • M. Sloth-Nielsen
    • 2
  1. 1.Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry and Psychology SectionKarolinska HospitalStockholmSweden
  2. 2.Novo Nordisk A/SMåløvDenmark

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