High 5-HT2 receptor occupancy in clozapine treated patients demonstrated by PET.
The clinical benefit of the atypical antipsychotic drug clozapine may be related to a combined effect on D2 and 5-HT2 receptors. To examine the basis for this hypothesis, positron emission tomography (PET) and the radioligand [11C]N-methylspiperone were used to determine cortical 5-HT2 receptor occupancy in three psychotic patients treated with 125 mg, 175mg and 200mg clozapine daily. The uptake of [11C]N-methylspiperone in the frontal cortex was very low compared to that in neuroleptic naive schizophrenic patients. 5-HT2 receptor occupancy calculated in the clozapine treated patients was 84%, 87% and 90%. The results show that clinical treatment with clozapine induces a high 5-HT2 receptor occupancy in psychotic patients at a low dose level.
Department of Psychiatry and Psychology, Karolinska Hospital, Stockholm, Sweden.
A L
AL
Nordström
L
L
Farde
C
C
Halldin
D000328:Adult; D014150:Antipsychotic Agents / Q000493:pharmacokinetics; D003024:Clozapine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000033:anatomy & histology / Q000378:metabolism; D011618:Psychotic Disorders / Q000188:drug therapy / Q000378:metabolism; D020891:Raclopride; D011985:Receptors, Serotonin / Q000378:metabolism*; D012457:Salicylamides / Q000493:pharmacokinetics; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D013134:Spiperone / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D011985:Receptors, Serotonin; D012457:Salicylamides; D020891:Raclopride; D013134:Spiperone; C039167:3-N-methylspiperone; D003024:Clozapine