| Title |
ITI-007 demonstrates brain occupancy at serotonin 5-HT2A and dopamine D2 receptors and serotonin transporters using positron emission tomography in healthy volunteers
|
|---|---|
| Published in |
Psychopharmacology, April 2015
|
| DOI | 10.1007/s00213-015-3922-1 |
| Pubmed ID | |
| Authors |
Robert E. Davis, Kimberly E. Vanover, Yun Zhou, James R. Brašić, Maria Guevara, Blanca Bisuna, Weiguo Ye, Vanessa Raymont, William Willis, Anil Kumar, Lorena Gapasin, D. Ronald Goldwater, Sharon Mates, Dean F. Wong |
| Abstract |
Central modulation of serotonin and dopamine underlies efficacy for a variety of psychiatric therapeutics. ITI-007 is an investigational new drug in development for treatment of schizophrenia, mood disorders, and other neuropsychiatric disorders. The purpose of this study was to determine brain occupancy of ITI-007 at serotonin 5-HT2A receptors, dopamine D2 receptors, and serotonin transporters using positron emission tomography (PET) in 16 healthy volunteers. Carbon-11-MDL100907, carbon-11-raclopride, and carbon-11-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) (carbon-11-DASB) were used as the radiotracers for imaging 5-HT2A receptors, D2 receptors, and serotonin transporters, respectively. Brain regions of interest were outlined using magnetic resonance tomography (MRT) with cerebellum as the reference region. Binding potentials were estimated by fitting a simplified reference tissue model to the measured tissue-time activity curves. Target occupancy was expressed as percent change in the binding potentials before and after ITI-007 administration. Oral ITI-007 (10-40 mg) was safe and well tolerated. ITI-007 rapidly entered the brain with long-lasting and dose-related occupancy. ITI-007 (10 mg) demonstrated high occupancy (>80 %) of cortical 5-HT2A receptors and low occupancy of striatal D2 receptors (~12 %). D2 receptor occupancy increased with dose and significantly correlated with plasma concentrations (r (2) = 0.68, p = 0.002). ITI-007 (40 mg) resulted in peak occupancy up to 39 % of striatal D2 receptors and 33 % of striatal serotonin transporters. The results provide evidence for a central mechanism of action via dopaminergic and serotonergic pathways for ITI-007 in living human brain and valuable information to aid dose selection for future clinical trials. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 57 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 57 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 13 | 23% |
| Student > Bachelor | 10 | 18% |
| Student > Master | 8 | 14% |
| Student > Ph. D. Student | 4 | 7% |
| Student > Doctoral Student | 2 | 4% |
| Other | 5 | 9% |
| Unknown | 15 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 14% |
| Neuroscience | 8 | 14% |
| Psychology | 6 | 11% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 9% |
| Biochemistry, Genetics and Molecular Biology | 3 | 5% |
| Other | 7 | 12% |
| Unknown | 20 | 35% |
Attention Score in Context
This research output has an Altmetric Attention Score of 12. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 December 2023.
All research outputs
#2,852,185
of 24,041,016 outputs
Outputs from Psychopharmacology
#700
of 5,460 outputs
Outputs of similar age
#36,733
of 268,642 outputs
Outputs of similar age from Psychopharmacology
#5
of 49 outputs
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