Psychopharmacology

, Volume 145, Issue 1, pp 76–81

Brain 5-HT2A receptor occupancy of deramciclane in humans after a single oral administration – a positron emission tomography study

  • H. Kanerva
  • Harry Vilkman
  • Kjell Någren
  • Olavi Kilkku
  • Mikko Kuoppamäki
  • Erkka Syvälahti
  • Jarmo Hietala
ORIGINAL INVESTIGATION

DOI: 10.1007/s002130051034

Cite this article as:
Kanerva, H., Vilkman, H., Någren, K. et al. Psychopharmacology (1999) 145: 76. doi:10.1007/s002130051034

Abstract

Rationale: Deramciclane fumarate is a new 5-HT2A and 5-HT2C receptor antagonist with putative anxiolytic effects. In the present study the binding of deramciclane to serotonin 5-HT2A receptors in frontal cortex of healthy male volunteers was studied using [11C]-N-methyl spiperone ([11C]-NMSP) and positron emission tomography. Methods: The receptor occupancy percentage was assessed by the means of inhibition of [11C]-NMSP from the 5-HT2A receptors in the frontal cortex. Single oral doses of 20, 50 and 150 mg deramciclane were given to three subjects at each dose level (total n = 9). The receptor occupancy was measured before deramciclane and at 3 and 6 h post-dosing except at the 20 mg dose level where only the 3-h measurement was done. The occupancy percentage was calculated with the ratio method using cerebellum as a reference area. Results: Deramciclane inhibited [11C]-NMSP binding dose and concentration dependently. However, deramasciclane inhibited maximally only 52% of the [11C]-NMSP binding in the frontal cortex, indicating a non-5-HT2A receptor binding component of this radioligand in frontal cortex. On average, specific [11C]-NMSP binding cerebellum ratios below 0.355 were not possible to achieve in this population. The 52% inhibition was regarded to represent near 100% 5-HT2A receptor occupancy. The 50 and 90% receptor occupancies were reached at deramciclane plasma concentrations of 21 ng/ml and 70 ng/ml, respectively. Conclusions: Deramciclane penetrates the blood-brain barrier in humans. Deramciclane binds to the 5-HT2A receptors in the frontal cortex in a saturable manner in vivo. Consequently, the increase in deramciclane concentration in plasma above 70 ng/ml will not result in major increase in the 5-HT2A receptor occupancy in the brain.

Key words Deramciclane fumarate Positron emission tomography [11C]-NMSP Serotonin 

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • H. Kanerva
    • 1
  • Harry Vilkman
    • 2
  • Kjell Någren
    • 3
  • Olavi Kilkku
    • 1
  • Mikko Kuoppamäki
    • 4
  • Erkka Syvälahti
    • 2
  • Jarmo Hietala
    • 5
  1. 1.Orion Corporation, Orion Pharma, P.O. Box 65, FIN-02101 Espoo, FinlandFI
  2. 2.Department of Pharmacology and Clinical Pharmacology, University of Turku, Kiinamyllynkatu 10, FIN-20250 Turku, FinlandFI
  3. 3.PET Centre, University of Turku, Kiinamyllynkatu 10, FIN-20250 Turku, FinlandFI
  4. 4.Department of Neurology, Turku University Central Hospital, Kiinamyllynkatu 10, FIN-20250 Turku, FinlandFI
  5. 5.Department of Psychiatry, Turku University Central Hospital, Kiinamyllynkatu 10, FIN-20250 Turku, FinlandFI

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