F-15,599, also known as NLX-101, is a potent and selective 5-HT1A receptor full agonist.[1][2] It displays functional selectivity (also known as "biased agonism") by strongly activating 5-HT1A receptors in the postsynaptic prefrontal cortex while having little effect on somatodendritic autoreceptors in the raphe nucleus.[1][2] As a result, it has been touted as a preferential postsynaptic 5-HT1A receptor agonist and has been investigated as a novel potential antidepressant.[1][2][3]
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Routes of administration | Oral |
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Formula | C19H22ClF2N4O |
Molar mass | 395.86 g·mol−1 |
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In cognitive tests in rodent, F-15,599 attenuates memory deficits elicited by the NMDA receptor antagonist PCP, suggesting that it may improve cognitive function in disorders such as schizophrenia.[4]
A subsequent study showed that F-15,599 reduces breathing irregularity and apneas observed in mice with mutations of the MeCP2 gene.[5] Dysruption of MeCP2 gene expression underlies Rett syndrome, a debilitating neurodevelopmental orphan disease.
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.[6] and obtained orphan drug designation from the United States Food and Drug Administration (FDA)[7] and from the European Commission for this indication.[8]
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.[9] In June 2015, the Rett Syndrome Research Trust awarded a grant to Neurolixis to advance F-15599 to clinical development.[10]