F-15599
Chemical compound
From Wikipedia, the free encyclopedia
F-15,599, also known as NLX-101, is a potent and selective 5-HT1A receptor full agonist.[1][2] In addition, it displays functional selectivity, or biased agonism, by preferentially activating postsynaptic serotonin 5-HT1A receptors over somatodendritic serotonin 5-HT1A autoreceptors.[3][1][2] The drug has been investigated for potential use as a pharmaceutical drug in the treatment of conditions including depression, schizophrenia, cognitive disorders, Rett syndrome, and fragile X syndrome.[4]
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| Other names | F-15599; F15599; NLX-101; NLX101 |
| Routes of administration | Oral |
| Drug class | Serotonin 5-HT1A receptor agonist |
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| Metabolism | DB16936DB16936 |
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| Formula | C19H22ClF2N4O |
| Molar mass | 395.86 g·mol−1 |
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Pharmacology
Pharmacodynamics
In terms of its functional selectivity, the drug preferentially activates and phosphorylates ERK1/2 over receptor internalization or inhibition of adenylyl cyclase.[3] In addition, it preferentially activates the Gαi G protein subtype over the Gαo subtype.[3] As a result of its biased agonism for postsynaptic 5-HT1A receptors, F-15,599 shows regional selectivity in its central effects.[3] It mainly activates the prefrontal cortex, cingulate cortex, retrosplenial cortex, septum, and colliculi.[3] Conversely, the drug does not significantly alter cerebral blood flow in areas characterized by abundance of presynaptic serotonin 5-HT1A receptors, such as the raphe nucleus.[3][1][2]
F-15,599 has shown antidepressant-like, anxiolytic-like, antidyskinetic, procognitive, and antiaggressive effects in animals.[3][1][2][5] In cognitive tests in rodents, F-15,599 attenuates memory deficits elicited by the NMDA receptor antagonist phencyclidine (PCP), suggesting that it may improve cognitive function in disorders such as schizophrenia.[6] Another study found that F-15,599 reduces breathing irregularity and apneas observed in mice with mutations of the MeCP2 gene, a mouse model of Rett syndrome.[3][7]
History
F-15,599 was first described in the scientific literature by 2006.[8]
Clinical trials
F-15,599 was discovered and initially developed by Pierre Fabre Médicament, a French pharmaceuticals company. In September 2013, F-15,599 was out-licensed to Neurolixis, a California-based biotechnology company. Neurolixis announced that it intends to re-purpose F-15,599 for the treatment of Rett syndrome.[9] and obtained orphan drug designation from the United States Food and Drug Administration (FDA)[10] and from the European Commission for this indication.[11]
Researchers at the University of Bristol are investigating the activity of F-15599 in animal models of Rett Syndrome, with support from the International Rett Syndrome Foundation.[12] In June 2015, the Rett Syndrome Research Trust awarded a grant to Neurolixis to advance F-15599 to clinical development.[13]
As of September 2024, F-15,599 is in phase 1 clinical trials for fragile X syndrome.[4] Conversely, no recent development has been reported for depressive disorders or Rett syndrome and development has been discontinued for cognition disorders, mood disorders, and schizophrenia.[4]
See also
- Befiradol (F-13640; NLX-112)
- Eptapirone (F-11440)
- NLX-266
- TMU4142