|Systematic (IUPAC) name|
|Mol. mass||395.854 g/mol|
F-15,599, also known as NLX-101, is a very potent and highly 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 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.
- 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.
- 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.
- 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.
- 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.
- 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.