In vivo 5-HT2A receptor blockade by quetiapine: an R91150 single photon emission tomography study

Psychopharmacology (Berl). 2001 Aug;157(1):60-6. doi: 10.1007/s002130100761.

Abstract

Background: Atypical antipsychotic drugs are thought to show a high degree of 5-HT2A receptor blockade, which may prevent the emergence of extrapyramidal symptoms.

Method: 5-HT2A binding was estimated using 123I-5-I-R91150 and single photon emission tomography (SPET) in six schizophrenic subjects treated with quetiapine at a mean (+/-SD) daily dose of 350+/-123 mg for at least 5 weeks and a matched sample of six healthy volunteers. Clinical and side-effect ratings were performed at baseline and at the time of SPET scanning. The reference region approach was used to define a 5-HT2A binding index in the frontal and temporal cortex.

Results: Quetiapine treatment resulted in a significant decline in 5-HT2A receptor availability in the frontal cortex (mean 0.98+/-0.09) relative to healthy volunteers (mean 1.33+/-0.16). All patients showed improvements in clinical symptom or side-effect ratings. The mean frontal cortex:cerebellum ratio after quetiapine treatment was significantly negatively correlated with reduction in the Abnormal Involuntary Rating scale and Simpson-Angus scores (P<0.05 Bonferroni corrected), but not with the reduction in the scores from the scale for the assessment of positive symptoms, the scale for the assessment of negative symptoms, the Montgomery-Asberg depression rating scale or patient age.

Conclusion: Quetiapine treatment results in significant in vivo blockade of cortical 5-HT2A, similar to other atypical antipsychotic drugs. This effect may contribute to its placebo level extrapyramidal side-effect profile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dibenzothiazepines / adverse effects
  • Dibenzothiazepines / pharmacology*
  • Dibenzothiazepines / therapeutic use
  • Female
  • Frontal Lobe / metabolism
  • Humans
  • Iodine Radioisotopes
  • Male
  • Piperidines / metabolism*
  • Prospective Studies
  • Quetiapine Fumarate
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Dopamine D2 / analysis
  • Receptors, Serotonin / analysis
  • Receptors, Serotonin / drug effects*
  • Schizophrenia / drug therapy
  • Serotonin Antagonists / pharmacology*
  • Tomography, Emission-Computed, Single-Photon*

Substances

  • Dibenzothiazepines
  • Iodine Radioisotopes
  • Piperidines
  • R 91150
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Dopamine D2
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Quetiapine Fumarate