Chemistry:F-15,599

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Short description: Chemical compound
F-15,599
F-15,599.svg
Clinical data
Routes of
administration		Oral
Legal status
Legal status
  • Investigational
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
Chemical and physical data
FormulaC19H22ClF2N4O
Molar mass395.86 g·mol−1
3D model (JSmol)
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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]

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]

See also

References

  1. ↑ 1.0 1.1 1.2 "High-efficacy 5-HT1A agonists for antidepressant treatment: a renewed opportunity". Journal of Medicinal Chemistry 50 (20): 5024–33. October 2007. doi:10.1021/jm070714l. PMID 17803293. 
  2. ↑ 2.0 2.1 2.2 "Signal transduction and functional selectivity of F15599, a preferential post-synaptic 5-HT1A receptor agonist". British Journal of Pharmacology 156 (2): 338–53. January 2009. doi:10.1111/j.1476-5381.2008.00001.x. PMID 19154445. 
  3. ↑ "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. November 2010. doi:10.1017/S1461145709991222. PMID 20059805. 
  4. ↑ "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. September 2010. doi:10.1016/j.euroneuro.2010.04.005. PMID 20488670. 
  5. ↑ "A selective 5-HT1a receptor agonist improves respiration in a mouse model of Rett syndrome". Journal of Applied Physiology 115 (11): 1626–33. December 2013. doi:10.1152/japplphysiol.00889.2013. PMID 24092697. 
  6. ↑ http://neurolixis.com/images/stories/nlx_pf_license_23sept13.pdf[full citation needed]
  7. ↑ "Enforcement Reports". http://www.accessdata.fda.gov/scripts/opdlisting/oopd/OOPD_Results_2.cfm?Index_Number=410613. 
  8. ↑ "Public Health - European Commission". http://ec.europa.eu/health/documents/community-register/html/o1242.htm. 
  9. ↑ "April: Rett syndrome research | News and features | University of Bristol". http://www.bristol.ac.uk/news/2014/april/rett-syndrome-research.html. 
  10. ↑ "RSRT Awards $530,000 to Neurolixis for Clinical Development of NLX-101". 24 June 2015. https://rettsyndrome.wordpress.com/2015/06/24/rsrt-awards-530000-to-neurolixis-for-clinical-development-of-nlx-101/. 

External links



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