Distribution of remoxipride to the human brain and central D2-dopamine receptor binding examined in vivo by PET.

Remoxipride is a new antipsychotic drug that binds selectively to the D2-dopamine receptor subtype as demonstrated in animal studies in vitro and in vivo. It is generally assumed that the antipsychotic effect of neuroleptic drugs is mediated by blockade of dopamine receptors. The aim of the present study was to use positron emission tomography (PET) and the ligand [11C] raclopride to examine the central D2-dopamine receptor occupancy in man during oral administration of remoxipride. After oral administration of remoxipride 100 mg three times daily to a healthy male subject there was a 73% central D2-dopamine receptor occupancy. In a schizophrenic patient treated with remoxipride 200 mg twice daily there was a 71% occupancy. These occupancy values are similar to the values of 65-85% previously found in a series of patients treated with neuroleptics representative of all currently used chemical classes. In a separate experiment, remoxipride was labelled with 11C and injected intravenously and the distribution of radioactivity to the brain examined. Radioactivity appeared in the brain during the first minutes after injection and 4.5 min after injection it accounted for 0.8% of the total radioactivity injected, thus indicating that [11C]remoxipride had rapidly passed through the blood-brain barrier.