Time Course of 5-HT2A Receptor Occupancy in the Human Brain after a Single Oral Dose of the Putative Antipsychotic Drug MDL 100,907 Measured by Positron Emission Tomography

Authors:
  • FYF Yokoi
    F Yokoi
  • SOS J Offord
    S J Offord
  • HRH T Ravert
    H T Ravert
  • RDR F Dannals
    R F Dannals
  • JSJ K Salzmann
    J K Salzmann
  • SSS Szymanski
    S Szymanski
  • PWP D Wilson
    P D Wilson
  • DHD R Howard
    D R Howard
  • DWD F Wong
    D F Wong
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Abstract
MDL 100,907 is a potent and selective antagonist of 5-HT2A serotonin receptors. Animals studies suggest that MDL 100,907 may behave as an atypical antipsychotic drug. Positron emission tomograph (PET) using [11C]NMSP as the radiotracer was used to define the time course of 5-HT2 receptor occupancy in the human frontal cerebral cortex after a single oral dose of MDL 100,907 (10 or 20 mg) in nine healthy subjects. After the baseline scan each subject was studied three times post dosing at various time points. 5-HT2 occupancies were in the range of 70 and 90% after each dose. While the occupancy remains in this range over 24 hours after 20 mg MDL 100,907, it decreases by about 20% at 24 hours compared to the timepoint at 8 hours, when only 10 mg are administered (p < 0.05). Our results should allow determination of the appropriate dosing regimen for future trials in schizophrenic patients.