Unlocking the Therapeutic Potential of Ulotaront as a Trace Amine-Associated Receptor 1 Agonist for Neuropsychiatric Disorders
All antipsychotics currently used in clinic block D2 dopamine receptors. Trace amine-associated receptor 1 is emerging as a new therapeutic target for schizophrenia and several other neuropsychiatric disorders. SEP-363856 (International Nonproprietary Name: Ulotaront) is an investigational antipsych...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/7/1977 |
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| author | Savelii R. Kuvarzin Ilya Sukhanov Kirill Onokhin Konstantin Zakharov Raul R. Gainetdinov |
| author_facet | Savelii R. Kuvarzin Ilya Sukhanov Kirill Onokhin Konstantin Zakharov Raul R. Gainetdinov |
| author_sort | Savelii R. Kuvarzin |
| collection | DOAJ |
| description | All antipsychotics currently used in clinic block D2 dopamine receptors. Trace amine-associated receptor 1 is emerging as a new therapeutic target for schizophrenia and several other neuropsychiatric disorders. SEP-363856 (International Nonproprietary Name: Ulotaront) is an investigational antipsychotic drug with a novel mechanism of action that does not involve antagonism of dopamine D2 receptors. Ulotaront is an agonist of trace amine-associated receptor 1 and serotonin 5-HT1A receptors, but can modulate dopamine neurotransmission indirectly. In 2019, the United States Food and Drug Administration granted Breakthrough Therapy Designation for ulotaront for the treatment of schizophrenia. Phase 2 clinical studies indicated that ulotaront can reduce both positive and negative symptoms of schizophrenia without causing the extrapyramidal or metabolic side effects that are inherent to most currently used antipsychotics. At present, it is in phase 3 clinical development for the treatment of schizophrenia and is expected to be introduced into clinical practice in 2023–2024. Clinical studies evaluating the potential efficacy of ulotaront in Parkinson’s disease psychosis, generalized anxiety disorder, and major depressive disorder have also been started. The aim of this scoping review is to summarize all currently available preclinical and clinical evidence on the utility of ulotaront in the treatment of schizophrenia. Here, we show the main characteristics and distinctive features of this drug. Perspectives and limitations on the potential use of ulotaront in the pharmacotherapy of several other neuropsychiatric disorders are also discussed. |
| first_indexed | 2024-03-11T01:17:13Z |
| format | Article |
| id | doaj.art-ff4edba3210347a99e361d5d51064936 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T01:17:13Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-ff4edba3210347a99e361d5d510649362023-11-18T18:27:42ZengMDPI AGBiomedicines2227-90592023-07-01117197710.3390/biomedicines11071977Unlocking the Therapeutic Potential of Ulotaront as a Trace Amine-Associated Receptor 1 Agonist for Neuropsychiatric DisordersSavelii R. Kuvarzin0Ilya Sukhanov1Kirill Onokhin2Konstantin Zakharov3Raul R. Gainetdinov4Institute of Translational Biomedicine, Saint Petersburg State University, 199034 Saint Petersburg, RussiaValdman Institute of Pharmacology, Pavlov Medical University, 197022 Saint Petersburg, RussiaInstitute of Translational Biomedicine, Saint Petersburg State University, 199034 Saint Petersburg, RussiaAccellena Research and Development Inc., 199106 Saint Petersburg, RussiaInstitute of Translational Biomedicine, Saint Petersburg State University, 199034 Saint Petersburg, RussiaAll antipsychotics currently used in clinic block D2 dopamine receptors. Trace amine-associated receptor 1 is emerging as a new therapeutic target for schizophrenia and several other neuropsychiatric disorders. SEP-363856 (International Nonproprietary Name: Ulotaront) is an investigational antipsychotic drug with a novel mechanism of action that does not involve antagonism of dopamine D2 receptors. Ulotaront is an agonist of trace amine-associated receptor 1 and serotonin 5-HT1A receptors, but can modulate dopamine neurotransmission indirectly. In 2019, the United States Food and Drug Administration granted Breakthrough Therapy Designation for ulotaront for the treatment of schizophrenia. Phase 2 clinical studies indicated that ulotaront can reduce both positive and negative symptoms of schizophrenia without causing the extrapyramidal or metabolic side effects that are inherent to most currently used antipsychotics. At present, it is in phase 3 clinical development for the treatment of schizophrenia and is expected to be introduced into clinical practice in 2023–2024. Clinical studies evaluating the potential efficacy of ulotaront in Parkinson’s disease psychosis, generalized anxiety disorder, and major depressive disorder have also been started. The aim of this scoping review is to summarize all currently available preclinical and clinical evidence on the utility of ulotaront in the treatment of schizophrenia. Here, we show the main characteristics and distinctive features of this drug. Perspectives and limitations on the potential use of ulotaront in the pharmacotherapy of several other neuropsychiatric disorders are also discussed.https://www.mdpi.com/2227-9059/11/7/1977SEP-363856antipsychotic agentsdopamineschizophreniaulotaronttrace amine-associated receptor 1 |
| spellingShingle | Savelii R. Kuvarzin Ilya Sukhanov Kirill Onokhin Konstantin Zakharov Raul R. Gainetdinov Unlocking the Therapeutic Potential of Ulotaront as a Trace Amine-Associated Receptor 1 Agonist for Neuropsychiatric Disorders Biomedicines SEP-363856 antipsychotic agents dopamine schizophrenia ulotaront trace amine-associated receptor 1 |
| title | Unlocking the Therapeutic Potential of Ulotaront as a Trace Amine-Associated Receptor 1 Agonist for Neuropsychiatric Disorders |
| title_full | Unlocking the Therapeutic Potential of Ulotaront as a Trace Amine-Associated Receptor 1 Agonist for Neuropsychiatric Disorders |
| title_fullStr | Unlocking the Therapeutic Potential of Ulotaront as a Trace Amine-Associated Receptor 1 Agonist for Neuropsychiatric Disorders |
| title_full_unstemmed | Unlocking the Therapeutic Potential of Ulotaront as a Trace Amine-Associated Receptor 1 Agonist for Neuropsychiatric Disorders |
| title_short | Unlocking the Therapeutic Potential of Ulotaront as a Trace Amine-Associated Receptor 1 Agonist for Neuropsychiatric Disorders |
| title_sort | unlocking the therapeutic potential of ulotaront as a trace amine associated receptor 1 agonist for neuropsychiatric disorders |
| topic | SEP-363856 antipsychotic agents dopamine schizophrenia ulotaront trace amine-associated receptor 1 |
| url | https://www.mdpi.com/2227-9059/11/7/1977 |
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