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Vilazodone, sold under the brand name Viibryd among others, is a medication used to treat major depressive disorder. It is classified as a serotonin modulator and is taken by mouth.
Lubazodone is an experimental antidepressant which was under development by Yamanouchi for the treatment for major depressive disorder in the late 1990s and early 2000s but was never marketed. It acts as a serotonin reuptake inhibitor and 5-HT2A receptor antagonist, and hence has the profile of a serotonin antagonist and reuptake inhibitor (SARI). The drug has good selectivity against a range of other monoamine receptors, with its next highest affinities being for the α1-adrenergic receptor and the 5-HT2C receptor. Lubazodone is structurally related to trazodone and nefazodone, but is a stronger serotonin reuptake inhibitor and weaker as a 5-HT2A receptor antagonist in comparison to them and is more balanced in its actions as a SARI. It reached phase II clinical trials for depression, but development was discontinued in 2001 reportedly due to the "erosion of the SSRITooltip selective serotonin reuptake inhibitor market in the United States".
Litoxetine (developmental code names SL 81-0385, IXA-001) is an antidepressant which was under clinical development for the treatment of depression in the early 1990s but was never marketed. It acts as a potent serotonin reuptake inhibitor (Ki for SERTTooltip serotonin transporter = 7 nM) and modest 5-HT3 receptor antagonist (Ki = 315 nM). It has antiemetic activity, and unlike the selective serotonin reuptake inhibitors (SSRIs), appears to have a negligible incidence of nausea and vomiting. The drug is structurally related to indalpine. Development of litoxetine for depression was apparently ceased in the late 1990s. However, as of March 2017, development of litoxetine has been reinitiated and the drug is now in the phase II stage for the treatment of urinary incontinence.
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Centanafadine (INN) (former developmental code name EB-1020) is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) that began its development with Euthymics Bioscience after they acquired DOV Pharmaceutical. It was developed as a treatment for attention-deficit hyperactivity disorder (ADHD) and inhibits the reuptake of norepinephrine, dopamine, and serotonin with an IC50 ratio of 1:6:14, respectively. In 2011, Euthymics Bioscience spun off its development of centanafadine to a new company called Neurovance. In March 2017, Otsuka Pharmaceutical acquired Neurovance and the rights to centanafadine. As of January 2018, Otsuka's pipeline indicates it is in Phase II and III clinical trials for a number of different applications to medical conditions.
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Cericlamine is a potent and moderately selective serotonin reuptake inhibitor (SSRI) of the amphetamine family that was investigated as an antidepressant for the treatment of depression, anxiety disorders, and anorexia nervosa by Jouveinal but did not complete development and was never marketed. It reached phase III clinical trials in 1996 before development was discontinued in 1999.
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Ampreloxetine is a selective norepinephrine reuptake inhibitor (NRI) which is under development for the treatment of symptomatic neurogenic orthostatic hypotension (NOH).
SNG-12, also known as Synapsinae, is a glycine transporter 1 (GlyT1) inhibitor, or a glycine reuptake inhibitor, which is under development for the treatment of psychotic disorders, dementia, depressive disorders, and suicidal ideation. As of September 2022, it is in phase 3 clinical trials for depressive disorders and suicidal ideation and is in phase 2 clinical rials for psychotic disorders and dementia. The drug is under development by SyneuRx. It is described as a small molecule, but its chemical structure does not appear to have been disclosed.
Pegipanermin is a tumor necrosis factor α (TNFα) inhibitor which is under development for the treatment of Alzheimer's disease, mild cognitive impairment, major depressive disorder, and other indications. It is described as having potential anti-inflammatory effects. It is administered by subcutaneous injection.
ML-007 is a selective muscarinic acetylcholine M1 and M4 receptor agonist which is under development for the treatment of schizophrenia, psychotic disorders, and dyskinesias. It is being developed in combination with a peripherally selective muscarinic acetylcholine receptor antagonist (also known as ML-007/peripherally acting anticholinergic or ML-007/PAC). The drug is taken by mouth.
OPC-64005 is a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), or "triple reuptake inhibitor" (TRI), which is under development for the treatment of major depressive disorder. It was also under development for the treatment of attention deficit hyperactivity disorder (ADHD), but development for this indication was discontinued. It is taken by mouth.
References
- 1 2 3 4 "SYT 510". AdisInsight. 22 January 2024. Retrieved 15 August 2024.
- 1 2 3 "Delving into the Latest Updates on SYT-510 with Synapse". Synapse. 4 August 2024. Retrieved 15 August 2024.
- 1 2 3 Gertsch J, Chicca A (July 2024). "CNS Drug Discovery in Academia: Where Basic Research Meets Innovation". ChemBioChem: e202400397. doi:10.1002/cbic.202400397. PMID 38958639.
Five years after incorporation, Synendos Therapeutics has completed non-clinical development of the [selective endocannabinoid reuptake inhibitor (SERI)] drug candidate SYT-510 and has initiated Phase 1 clinical development in healthy volunteers, marking the significant transition into a clinical stage biotech company. The mission of Synendos is to develop breakthrough safe and effective therapies for neurological and neuropsychiatric disorders through modulation of the [endocannabinoid system (ECS)] with SERIs to enable restoration of the natural functioning of the brain.
- 1 2 3 Therapeutics, Synendos (18 January 2024). "Synendos Therapeutics AG Granted EMA Clinical Trial Authorisation for first-in-class Endocannabinoid System modulator, SYT-510". PR Newswire. Retrieved 15 August 2024.
