Flibanserin
[CAS# 167933-07-5]

Identification

• Classification: API >> Hormone and endocrine-regulating drugs >> Pancreatic hormones and other blood sugar regulating drugs
• Name: Flibanserin
• Synonyms: 3-[2-[4-[4-(Trifluoromethyl)phenyl]piperazin-1-yl]ethyl]-1H-benzimidazol-2-one
• Molecular Formula: C₂₀H₂₁F₃N₄O
• Molecular Weight: 390.40
• CAS Registry Number: 167933-07-5
• EC Number: 643-002-2
• SMILES: C1CN(CCN1CCN2C3=CC=CC=C3NC2=O)C4=CC=CC(=C4)C(F)(F)F

Properties

• Solubilkity: 10 mM (DMSO)

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Risk Statements: H301-H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P316-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	3	H301
Specific target organ toxicity - single exposure	STOT SE	3	H335
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412

Discovery and Applications

Flibanserin is a compound with the chemical formula C20H21F3N4O that is primarily used to treat hypoactive sexual desire disorder (HSDD) in premenopausal women. The drug, sold under the brand name Addyi, has attracted much attention for its unique mechanism of action and its role in treating a condition that severely affects women's quality of life.

The discovery of flibanserin can be traced back to research work at the German pharmaceutical company Boehringer Ingelheim in the early 2000s. Flibanserin was originally developed as an antidepressant and its potential to enhance sexual desire was discovered in clinical trials. Researchers noticed that while its antidepressant effects were modest, many female participants reported an increase in sexual desire and activity. This unexpected result shifted the focus of flibanserin's development toward treating HSDD, a condition characterized by a persistent lack of sexual desire that causes distress or difficulty in interpersonal relationships.

The mechanism of action of flibanserin is different from other sexual dysfunction treatments, such as those used to treat erectile dysfunction in men. It works by regulating neurotransmitters in the brain, specifically, increasing dopamine and norepinephrine levels while decreasing serotonin levels. Dopamine and norepinephrine are associated with sexual arousal, while serotonin can suppress sexual desire. By rebalancing these chemicals, flibanserin aims to restore sexual desire in women with HSDD.

The U.S. Food and Drug Administration (FDA) initially rejected flibanserin in 2010, citing concerns about its efficacy and side effects. However, after further research and a major campaign highlighting the lack of treatments for female sexual dysfunction, the FDA approved flibanserin in 2015. This approval marked an important milestone, as flibanserin became the first medication specifically approved for HSDD in premenopausal women.

In clinical practice, flibanserin is prescribed as a daily oral tablet. Studies have shown that flibanserin can increase the number of sexually satisfying events and reduce the distress associated with low sexual desire. However, the use of flibanserin may have side effects, including dizziness, drowsiness, nausea, fatigue, insomnia, and dry mouth. In addition, there are strict rules regarding drinking alcohol while taking flibanserin, as the combination of the two may cause severe hypotension and fainting.

The approval and subsequent use of flibanserin has sparked both support and controversy. Supporters argue that flibanserin addresses a significant unmet medical need, providing women with an option to treat a painful condition. However, critics have expressed concerns about its poor efficacy, side effects, and an extensive marketing campaign that sometimes obscures its clinical benefits.

Despite these controversies, flibanserin remains an important option for treating HSDD. Its development also highlights the broader issue of gender disparities in sexual health research and treatment options. By bringing attention to female sexual dysfunction, flibanserin paved the way for more research and development in this area, encouraging a more balanced approach to sexual health.

References

2023. Flibanserin in the treatment of hypoactive sexual desire disorder: a review of recent studies. Psychopharmacology, 240(6).
DOI: 10.1007/s00213-023-06501-9

2024. Recent advances in the synthesis and therapeutic applications of flibanserin. DARU Journal of Pharmaceutical Sciences, 32(1).
DOI: 10.1007/s40199-024-00543-w

2013. Synthesis and biological evaluation of flibanserin analogues as serotonin receptor modulators. Immunologic Research, 56(2-3).
DOI: 10.1007/s12026-013-8387-x