High 5-HT2 receptor occupancy in clozapine treated patients demonstrated by PET

Psychopharmacology (Berl). 1993;110(3):365-7. doi: 10.1007/BF02251294.

Abstract

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antipsychotic Agents / pharmacokinetics
  • Clozapine / pharmacokinetics*
  • Clozapine / therapeutic use
  • Dopamine Agonists / pharmacokinetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prefrontal Cortex / anatomy & histology
  • Prefrontal Cortex / metabolism
  • Psychotic Disorders / drug therapy
  • Psychotic Disorders / metabolism
  • Raclopride
  • Receptors, Serotonin / metabolism*
  • Salicylamides / pharmacokinetics
  • Schizophrenia / drug therapy
  • Schizophrenia / metabolism
  • Spiperone / analogs & derivatives
  • Spiperone / pharmacokinetics
  • Tomography, Emission-Computed

Substances

  • Antipsychotic Agents
  • Dopamine Agonists
  • Receptors, Serotonin
  • Salicylamides
  • Raclopride
  • Spiperone
  • 3-N-methylspiperone
  • Clozapine