In vivo 5-HT_2A receptor blockade by quetiapine

Abstract.

Background: Atypical antipsychotic drugs are thought to show a high degree of 5-HT_2A receptor blockade, which may prevent the emergence of extrapyramidal symptoms. Method: 5-HT_2A 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-HT_2A binding index in the frontal and temporal cortex. Results: Quetiapine treatment resulted in a significant decline in 5-HT_2A 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-HT_2A, similar to other atypical antipsychotic drugs. This effect may contribute to its placebo level extrapyramidal side-effect profile.