In vivo 5-HT2A receptor blockade by quetiapine: an R91150 single photon emission tomography study.
BACKGROUND
Atypical antipsychotic drugs are thought to show a high degree of 5-HT2A receptor blockade, which may prevent the emergence of extrapyramidal symptoms.


METHODS
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.


CONCLUSIONS
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.
Jones
H M
HM
Department of Psychological Medicine, Section of Neurochemical Imaging, Institute of Psychiatry, 1 Windsor Walk, Denmark Hill, London SE5 8AF, UK. hugh.jones@iop.kcl.ac.uk
Travis
M J
MJ
Mulligan
R
R
Bressan
R A
RA
Visvikis
D
D
Gacinovic
S
S
Ell
P J
PJ
Pilowsky
L S
LS
D000328:Adult; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D010880:Piperidines / Q000378:metabolism*; D011446:Prospective Studies; D000069348:Quetiapine Fumarate; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2 / Q000032:analysis; D011985:Receptors, Serotonin / Q000032:analysis / Q000187:drug effects*; D012559:Schizophrenia / Q000188:drug therapy; D012702:Serotonin Antagonists / Q000494:pharmacology*; D015899:Tomography, Emission-Computed, Single-Photon
D003987:Dibenzothiazepines; D007457:Iodine Radioisotopes; D010880:Piperidines; C105020:R 91150; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D000069348:Quetiapine Fumarate