Striatal and Extrastriatal Dopamine D2 Receptor Occupancy by a Novel Antipsychotic, Blonanserin: A PET Study With [11C]Raclopride and [11C]FLB 457 in Schizophrenia

  title={Striatal and Extrastriatal Dopamine D2 Receptor Occupancy by a Novel Antipsychotic, Blonanserin: A PET Study With [11C]Raclopride and [11C]FLB 457 in Schizophrenia},
  author={Amane Tateno and Ryosuke Arakawa and Masaki Okumura and Hajime Fukuta and Kazuyoshi Honjo and Keiichi Ishihara and Hiroshi Nakamura and Shinichiro Kumita and Yoshiro Okubo},
  journal={Journal of Clinical Psychopharmacology},
Abstract Blonanserin is a novel antipsychotic with high affinities for dopamine D2 and 5-HT2A receptors, and it was recently approved for the treatment of schizophrenia in Japan and Korea. Although double-blind clinical trials have demonstrated that blonanserin has equal efficacy to risperidone, and with a better profile especially with respect to prolactin elevation, its profile of in vivo receptor binding has not been investigated in patients with schizophrenia. Using positron emission… 

Comparison of Dopamine D3 and D2 Receptor Occupancies by a Single Dose of Blonanserin in Healthy Subjects: A Positron Emission Tomography Study With [11C]-(+)-PHNO

A single dose of 12 mg blonanserin occupied D3 receptor to the same degree as D2 receptor in vivo, consistent with previous studies that reported that some of the pharmacological effect of blonANSerin is mediated via D3 receptors antagonism.

In vivo activity of modafinil on dopamine transporter measured with positron emission tomography and [¹⁸F]FE-PE2I.

It was showed that DAT occupancy by modafinil was close to that of methylphenidate, indicating that modaf inil may be near the same level as methyl phenidate in relation to abuse liability in terms of dopaminergic transmission.

Striatal Dopamine D2 Receptor Occupancy Induced by Daily Application of Blonanserin Transdermal Patches: Phase II Study in Japanese Patients With Schizophrenia

Boonserin patches have lower diurnal variability in occupancy than blonanserin tablets, and patches at doses of 40mg/d and 80 mg/d appear to be a suitable alternative for blonananser in tablets at dose of 8 mg/ d and 16 mg/D, respectively.

Effect of DL-Methylephedrine on Dopamine Transporter Using Positron Emission Tomography With [18F]FE-PE2I

It is suggested that a clinical daily dose of dl-methylephedrine may exceed the doping regulation value according to urine concentration; however, it was considered that at least the central excitatory effect mediated by DAT inhibition was not observed at the daily dose.

Prediction of Corresponding Dose of Transdermal Blonanserin to Oral Dose Based on Dopamine D2 Receptor Occupancy

Predicted D2 occupancy suggested that a 40- to 80- mg/d blonanserin transdermal patch dose corresponds to an 8- to 24-mg/d oral dose for the treatment of schizophrenia.

Blonanserin, a Novel Antipsychotic, Is Suitable for Treating Schizophrenia Associated With Hyperprolactinemia: A Case Series

Switching to blonanserin can reverse medication-induced prolactin elevations found in female patients— and blonANSerin is a suitable antipsychotic for schizophrenic patients.

The Pharmacokinetic and Safety Profiles of Blonanserin in Healthy Chinese Volunteers After Single Fasting Doses and Single and Multiple Postprandial Doses

It is suggested that food intake not only increases the bioavailability of blonanserin but differently affects the pharmacokinetics of its metabolite over parent compound ratio after single and multiple postprandial administrations.

PET technology for drug development in psychiatry

In order to evaluate new drug targets for disease conditions such as negative symptoms/cognitive impairment of schizophrenia and treatment‐resistant depression, new PET radioligands need to be developed concurrently with the drug development.



Striatal Vs Extrastriatal Dopamine D2 Receptors in Antipsychotic Response—A Double-Blind PET Study in Schizophrenia

D dopamine D2 blockade within specific regions of the striatum may be most critical for ameliorating psychosis in schizophrenia, when combined with the preclinical data implicating the mesolimbic striatum in antipsychotic response.

Dose–Occupancy Study of Striatal and Extrastriatal Dopamine D2 Receptors by Aripiprazole in Schizophrenia with PET and [18F]Fallypride

Correlations of ratings of clinical improvement with regional occupancy suggest that aripiprazole, as do other antipsychotics, benefits positive symptoms of schizophrenia most directly through its modulation of striatal rather than cortical or other extrastriatal dopamine activity.

No regional difference in dopamine D2 receptor occupancy by the second-generation antipsychotic drug risperidone in humans: a positron emission tomography study.

A simulation study showed that non-negligible specific binding in the reference region (cerebellum), could cause systemic underestimation of occupancy in [11C]FLB 457 PET studies, indicating that occupancies in both the striatum and extrastriatum may not have differed.

Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia

The data from this study suggest that paliperidone ER at 6–9 mg provides an estimated level of dopamine D2 receptor occupancy between 70–80% and that the magnitude of Parkinson's disease-like symptoms is similar between the striatum and temporal cortex.

Carbon-11-FLB 457: a radioligand for extrastriatal D2 dopamine receptors.

  • C. HalldinL. Farde C. Swahn
  • Biology, Chemistry
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine
  • 1995
Carbon-11-FLB 457 should be a useful PET ligand for quantitative examination of D2 dopamine receptors in extrastriatal regions in the human brain.

Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia.

The study confirms that D(2) occupancy is an important mediator of response and side effects in antipsychotic treatment, and is consistent with a "target and trigger" hypothesis of antipsychotics action.

Decreased thalamic D2/D3 receptor binding in drug-naive patients with schizophrenia: a PET study with [11C]FLB 457.

The preliminary finding of low thalamic D2/D3 BP in patients strengthens the hypothesis that the thalamus is a key region in the pathophysiology of schizophrenia and provides additional support to the view that the age effect on D2-D3 receptors differ between brain regions.

Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects.

This finding indicates that neuroleptic-induced extrapyramidal syndromes are related to the degree of central D2 occupancy induced in the basal ganglia of drug-treated schizophrenic patients and demonstrates that clozapine is also "atypical" with respect to the central D1 occupancy in patients.

Time course of dopamine D2 receptor occupancy by clozapine with medium and high plasma concentrations