D2 and 5HT2A receptor occupancy of different doses of quetiapine in schizophrenia: a PET study

  title={D2 and 5HT2A receptor occupancy of different doses of quetiapine in schizophrenia: a PET study},
  author={Ola Gefvert and Tommie Lundberg and I-M. Wieselgren and Mats Bergstr{\"o}m and Bengt L{\aa}ngstr{\"o}m and Frits-axel Wiesel and Leif H. Lindstr{\"o}m},
  journal={European Neuropsychopharmacology},

Dopamine D2/3 receptor occupancy by quetiapine in striatal and extrastriatal areas.

Taken together, quetiapine shows preferential extrastriatal binding at D2/3Rs; the extent of this difference is comparable to that previously described for clozapine.

Dopamine D2 receptor occupancy of lumateperone (ITI-007): a Positron Emission Tomography Study in patients with schizophrenia

D2RO at plasma steady state of 60 mg ITI-007, a dose that previously demonstrated antipsychotic efficacy in a controlled trial, was determined and likely contributes to the favorable safety and tolerability profile of lumateperone with reduced risk for movement disorders and hyperprolactinemia.

Pharmacokinetics and time-course of D2 receptor occupancy induced by atypical antipsychotics in stabilized schizophrenic patients

D2RO pattern over time was stable for risperidone, olanzapine and clozapine but fluctuating for quetiapine, suggesting that clinical response to these AP may be maintained with D2RO below 65%.

PET studies on the mechanism of monoaminergic drugs

Positron emission tomography was used to assess the pharmacological effects of two drugs representing the major classes of antipsychotic and antidepressant drugs and the effect of age on 5-HT1B receptor availability was examined, highlighting the importance of using age-matched controls in future clinical studies on the 5- HT1B receptors.

Contribution of SPECT Measurements of D2 and 5-HT2A Occupancy to the Clinical Development of the Antipsychotic SB-773812

In patients with schizophrenia, D2 occupancy levels induced by a single dose were maintained over time, indicating that once-daily dosing regimens are appropriate, and pharmacokinetics–receptor occupancy analysis provided guidance for the selection of a clinically effective dose, supporting progression in phase II.

The Striatal and Extrastriatal D2/D3 Receptor-Binding Profile of Clozapine in Patients with Schizophrenia

The occupancy of D2/D3 dopamine receptors by clozapine in patients with schizophrenia was determined to test the hypothesis that clozAPine binds preferentially to extrastriatal dopamine receptors.

Cortical dopamine D2/D3 receptors are a common site of action for antipsychotic drugs — An original patient data meta-analysis of the SPET and PET in vivo receptor imaging literature

It is concluded that cortical dopamine D(2)/D(3) receptor occupancy is involved in antipsychotic efficacy, with striatal D( 2)/D (3) occupancy having a likely therapeutic role while also inducing EPSE.

Quetiapine: preclinical studies, pharmacokinetics, drug interactions, and dosing.

In animal models, imaging studies with positron emission tomography confirm significant differences between quetiapine and typical antipsychotics that may be indicative of their differences in mechanism of action and propensity for producing EPS.

Discovery of Nonracemic Amisulpride to Maximize Benefit/Risk of 5‐HT7 and D2 Receptor Antagonism for the Treatment of Mood Disorders

An 85:15 ratio is found that maximizes the potential for antidepressant benefit of aramisulpride via 5-HT7R and reduces esamisULpride to minimize D2R-related extrapyramidal side effects while still retaining D1R-mediated effects predicted to provide benefit in bipolar depression.

Dopamine D2 Occupancy as a Biomarker for Antipsychotics: Quantifying the Relationship with Efficacy and Extrapyramidal Symptoms

Generic mathematical models developed for predicting antipsychotic efficacy and EPS tolerability based on D2 receptor occupancy were used to aid dose selection for asenapine phase II and III trials and can be envisaged as a dose selection tool for new antipsychotics with D2 antagonist properties in the treatment of schizophrenia.



5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation.

Olanzapine is a potent 5- HT2 blocker and shows a higher 5-HT2 than D2 occupancy at all doses, however, its D1 occupancy is higher than that of clozapine and similar to that of risperidone.

A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy.

The data suggest that transient D2 occupancy may be sufficient for its antipsychotic effect, and future studies controlling for nonpharmacological effects as well as activities on other receptors will be necessary to confirm this suggestion.

Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia.

Clozapine, at doses known to be effective in routine clinical settings, showed a D 2 occupancy clearly lower than that of typical antipsychotics, while risperidone and olanzapine at their usual clinical doses gave the same level of D2 occupancy as low-dose typical antippsychotics.

Time course of central nervous dopamine-D2 and 5-HT2 receptor blockade and plasma drug concentrations after discontinuation of quetiapine (Seroquel®) in patients with schizophrenia

PET data shows that quetiapine has a relatively low affinity for dopamine D2 receptors, with an occupancy half-life (10 h), which was about twice as long as that for plasma, which could suggest that the combination of D2/5HT2 receptor blockade contributes to the antipsychotic effect and a low incidence of EPS seen with quetuapine in comparative phase three trials.

Suggested minimal effective dose of risperidone based on PET-measured D2 and 5-HT2A receptor occupancy in schizophrenic patients.

To achieve this, resperidone, 4 mg/day, should be a suitable initial dose for antipsychotic effect with a minimal risk of extrapyramidal side effects in most patients.

The ratios of serotonin2 and dopamine2 affinities differentiate atypical and typical antipsychotic drugs.

Cluster analysis identified that the 5-HT2/D2 ratio was the most successful means of utilizing this data to classify typical and atypical antipsychotic drugs correctly, and a 92 percent accuracy was achieved.

The Importance of Serotonin-Dopamine Interactions in the Action of Clozapine

  • H. Meltzer
  • Psychology, Medicine
    British Journal of Psychiatry
  • 1992
The atypical antipsychotic drugs are best distinguished from the typical antipsychotics on the basis of the relationship between strong 5-HT2 and weak D2 affinities.

Quetiapine in patients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Seroquel Study Group.

Quetiapine is an effective antipsychotic with a favorable safety profile and the optimum dose is probably greater than 250 mg/d, which is well tolerated and did not induce extrapyramidal symptoms, sustained elevations of prolactin, or clinically significant changes in hematologic parameters.

Rapid release of antipsychotic drugs from dopamine D2 receptors: an explanation for low receptor occupancy and early clinical relapse upon withdrawal of clozapine or quetiapine.

The rapid release of clozapine and quetiapine from D2 receptors by endogenous dopamine may contribute to low D2 receptor occupancy and to early clinical relapse upon withdrawal of these medications.