F-15,599

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F-15,599, also known as NLX-101, is a very potent and highly 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

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External links


  1. ↑ 1.0 1.1 1.2 Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ 2.0 2.1 2.2 Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ http://neurolixis.com/images/stories/nlx_pf_license_23sept13.pdf[full citation needed]
  7. ↑ http://www.accessdata.fda.gov/scripts/opdlisting/oopd/OOPD_Results_2.cfm?Index_Number=410613[full citation needed]
  8. ↑ http://ec.europa.eu/health/documents/community-register/html/o1242.htm[full citation needed]
  9. ↑ http://www.bristol.ac.uk/news/2014/april/rett-syndrome-research.html
  10. ↑ https://rettsyndrome.wordpress.com/2015/06/24/rsrt-awards-530000-to-neurolixis-for-clinical-development-of-nlx-101/
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