|Chemical and physical data|
|Molar mass||395.86 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
F-15,599, also known as NLX-101, is a potent and selective 5-HT1A receptor full agonist. 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. As a result, it has been touted as a preferential postsynaptic 5-HT1A receptor agonist and has been investigated as a novel potential antidepressant.
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.
A subsequent study showed that F-15,599 reduces breathing irregularity and apneas observed in mice with mutations of the MeCP2 gene. 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. and obtained Orphan Drug designation from the United States Food and Drug Administration (FDA) and from the European Commission for this indication.
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. In June 2015, the Rett Syndrome Research Trust awarded a grant to Neurolixis to advance F-15599 to clinical development.
- Maurel JL, Autin JM, Funes P, Newman-Tancredi A, Colpaert F, Vacher B (October 2007). "High-efficacy 5-HT1A agonists for antidepressant treatment: a renewed opportunity". Journal of Medicinal Chemistry. 50 (20): 5024–33. doi:10.1021/jm070714l. PMID 17803293.
- Newman-Tancredi A, Martel JC, Assié MB, et al. (January 2009). "Signal transduction and functional selectivity of F15599, a preferential post-synaptic 5-HT1A receptor agonist". British Journal of Pharmacology. 156 (2): 338–53. doi:10.1111/j.1476-5381.2008.00001.x. PMC 2697830. PMID 19154445.
- Assié MB, Bardin L, Auclair AL, et al. (November 2010). "F15599, a highly selective post-synaptic 5-HT(1A) receptor agonist: in-vivo profile in behavioural models of antidepressant and serotonergic activity". The International Journal of Neuropsychopharmacology. 13 (10): 1285–98. doi:10.1017/S1461145709991222. PMID 20059805.
- Depoortère R, Auclair AL, Bardin L, Colpaert FC, Vacher B, Newman-Tancredi A (September 2010). "F15599, a preferential post-synaptic 5-HT1A receptor agonist: activity in models of cognition in comparison with reference 5-HT1A receptor agonists". European Neuropsychopharmacology. 20 (9): 641–54. doi:10.1016/j.euroneuro.2010.04.005. PMID 20488670. S2CID 22222213.
- Levitt ES, Hunnicutt BJ, Knopp SJ, Williams JT, Bissonnette JM (December 2013). "A selective 5-HT1a receptor agonist improves respiration in a mouse model of Rett syndrome". Journal of Applied Physiology. 115 (11): 1626–33. doi:10.1152/japplphysiol.00889.2013. PMC 3882741. PMID 24092697.
- http://neurolixis.com/images/stories/nlx_pf_license_23sept13.pdf[full citation needed]
- http://www.accessdata.fda.gov/scripts/opdlisting/oopd/OOPD_Results_2.cfm?Index_Number=410613[full citation needed]
- http://ec.europa.eu/health/documents/community-register/html/o1242.htm[full citation needed]