Evaluation of EMD 128 130 occupancy of the 5-HT1A and the D2 receptor:: a human PET study with [11C]WAY-100635 and [11C]raclopride

The use of so-called, atypical antipsychotic medication is becoming more widespread in the treatment of psychotic disorders. EMD 128 130 is a novel compound acting as an agonist at the 5-HT1A receptor, and as an antagonist at the dopamine-2 (D-2) receptor. This dual action may confer additional benefits over selective D-2 antagonists in the treatment of psychotic disorders. In this study, we investigated the occupancy of EMD 128 130 in vivo at the human D-2 and 5-HT1A receptors with positron emission tomography using the radiotracers [C-11]raclopride and [C-11]WAY-100635. Seven healthy volunteers were examined before and after 5 days of treatment with EMD 128 130, administered in an incremental dose building up to 50 mg, b.d. A significant occupancy was demonstrated at the human D-2 receptor (40% following a dose of 50 mg, b.d.) while there was no consistent effect observed at the 5-HT1A receptor, despite a similar affinity of EMD 128 130 for cloned human D-2 and 5-HT1A receptors, and the presence of typical, central 5-HT1A agonist side-effects. The differential effects of EMD 128 130 at the D-2 and the 5-HT1A receptor (antagonist at D-2 receptor, agonist at the 5-HT1A receptor) may explain the differences in occupancy observed.