Binding of antipsychotic drugs to cortical 5-HT2A receptors: a PET study of chlorpromazine, clozapine, and amisulpride in schizophrenic patients.
OBJECTIVE
This study examined the binding to cortical serotonin 5-HT2A receptors of conventional doses of the typical neuroleptic chlorpromazine in comparison with clozapine, the prototype atypical antipsychotic, and amisulpride, a specific dopamine D2-D3 blocker.


METHODS
Seventeen schizophrenic patients treated with chlorpromazine (75-700 mg/day), four treated with clozapine (200-600 mg/day), and five treated with amisulpride (200-1200 mg/day) were studied. Cortical 5-HT2A binding was estimated by reference to the values for 14 antipsychotic-free schizophrenic subjects with the use of positron emission tomography and [18F]setoperone, a high-affinity radioligand for cortical 5-HT2A receptors.


RESULTS
A dose-dependent decrease in the number of available cortical binding sites for [18F] setoperone was demonstrated in the chlorpromazine group; for the highest dose, there was a virtual lack of sites available for binding. A very low percentage of available binding sites was also observed in the clozapine-treated patients at all doses. This suggests a high level of 5-HT2A blockade with both clozapine and high doses of chlorpromazine. No significant binding of amisulpride to 5-HT2A receptors was detected.


CONCLUSIONS
A high level of 5-HT2A receptor blockade does not appear specific to clozapine in comparison with high doses of chlorpromazine, suggesting that the distinct clinical profiles of both drugs are unrelated to 5-HT2A blockade itself.
Trichard
C
C
Institut National de la Santé et de la Recherche Médicale, Service Hospitalier Frédéric Joliot, Paris, France.
Paillère-Martinot
M L
ML
Attar-Levy
D
D
Recassens
C
C
Monnet
F
F
Martinot
J L
JL
D000293:Adolescent; D000328:Adult; D000077582:Amisulpride; D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D002746:Chlorpromazine / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003024:Clozapine / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D011744:Pyrimidinones; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D005462:Fluorine Radioisotopes; D011744:Pyrimidinones; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D013469:Sulpiride; D000077582:Amisulpride; C045359:setoperone; D003024:Clozapine; D002746:Chlorpromazine