F-15,599, also known as NLX-101, is a potent and selective 5-HT_1A receptor

full agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ag ...

. It displays

functional selectivity Functional selectivity (or “agonist trafficking”, “biased agonism”, “biased signaling”, "ligand bias" and “differential engagement”) is the ligand-dependent selectivity for certain signal transduction pathways relative to a referen ...

(also known as "biased agonism") by strongly activating 5-HT_1A receptors in the

postsynaptic Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA ...

while having little effect on

somatodendritic Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

autoreceptor An autoreceptor is a type of receptor located in the membranes of nerve cells. It serves as part of a negative feedback loop in signal transduction. It is only sensitive to the neurotransmitters or hormones released by the neuron on which the a ...

s in the raphe nucleus. As a result, it has been touted as a preferential postsynaptic 5-HT_1A receptor agonist and has been investigated as a novel potential

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness ...

. 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 Rett syndrome (RTT) is a genetic disorder that typically becomes apparent after 6–18 months of age and almost exclusively in females. Symptoms include impairments in language and coordination, and repetitive movements. Those affected often h ...

, 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 Neurolixis is a biopharmaceutical company focused on novel drugs for the treatment of human central nervous system diseases. Neurolixis Inc. was founded in 2011 by Mark A. Varney, PhD, and Adrian Newman-Tancredi, PhD, DSc. (Chief Executive Offi ...

, a California-based biotechnology company. Neurolixis announced that it intends to re-purpose F-15,599 for the treatment of

. and obtained

Orphan Drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment o ...

designation from the United States

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) and from the European Commission for this indication. Researchers at the

University of Bristol The University of Bristol is a Red brick university, red brick Russell Group research university in Bristol, England. It received its royal charter in 1909, although it can trace its roots to a Society of Merchant Venturers, Merchant Venturers' sc ...

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.

References

External links

F-15599 - AdisInsight
{{Serotonergics Amines Piperidines Pyrimidines Benzamides Chloroarenes Organofluorides 5-HT1A agonists Fluoroarenes

See also

References

External links