Flibanserin
Identification
- Summary
Flibanserin is a 5-HT receptor modulator used for the treatment of selected premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD).
- Brand Names
- Addyi
- Generic Name
- Flibanserin
- DrugBank Accession Number
- DB04908
- Background
Flibanserin is the first drug to be approved for hypoactive sexual desire disorder (HSDD) in premenopausal women by the FDA in August 2015. It was originally developed as an antidepressant medication by Boehringer Ingelheim, but showed lack of efficacy in trials and was further developed as a hypoactive sexual disorder drug by Sprout Pharmaceuticals. Flibanserin's mechanism of action is attributed to its high affinity for 5-HTA1 and 5-HTA2 receptors, displaying agonist activity on 5-HTA1 and antagonist on 5-HTA2, resulting in lowering of serotonin in the brain as well as an effect on increasing norepinephrine and dopamine neurotransmitters.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 390.4021
Monoisotopic: 390.166745929 - Chemical Formula
- C20H21F3N4O
- Synonyms
- Flibanserin
- External IDs
- BIMT 17
- BIMT 17 BS
- BIMT-17
- BIMT-17-BS
Pharmacology
- Indication
For the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Hypoactive sexual desire disorder •••••••••••• ••••••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Not Available
- Mechanism of action
Flibansetrin has high affinity for serotonin receptors in the brain: it acts as an agonist on 5-HT1A and an antagonist on 5-HT2A. In vivo, flibanserin binds equally to 5-HT1A and 5-HT2A receptors. However, under higher levels of brain 5-HT (i.e., under stress), flibanserin may occupy 5-HT2A receptors in higher proportion than 5-HT(1A) receptors. It may also moderately antagonize D4 (dopamine) receptors and 5-HT2B and 5-HTB2C. Its action on neurotransmitter receptors may contribute to reduction in serotonin levels and increase in dopamine and norepinephrine levels, all of which may play part in reward processing.
Target Actions Organism A5-hydroxytryptamine receptor 1A agonistHumans A5-hydroxytryptamine receptor 2A antagonistHumans ADopamine D4 receptor antagonistagonistHumans - Absorption
Flibanserin has an absolute oral availability of 33%.
- Volume of distribution
Not Available
- Protein binding
~98%, highly bound to proteins (mostly albumin) in serum.
- Metabolism
Metabolism is primarily via CYP3A4, slightly CYP2C19. Minimal involvement of CYP1A2, CYP2B6, CYP2C8, CYP2C9 or CYP2D6. At least 35 metabolites of flibanserin are produced, 2 of which reach plasma concentrations as high as parent drug, however they are pharmacologically inactive.
- Route of elimination
Elimination via feces (51%) and urine (44%) following a single oral 50 mg dose of flibanserin solution.
- Half-life
≈11 hours
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 2C19 CYP2C19*2A Not Available 681G>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*2B Not Available 681G>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*3 Not Available 636G>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*4 Not Available 1A>G Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*5 Not Available 1297C>T Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*6 Not Available 395G>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*7 Not Available 19294T>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*22 Not Available 557G>C / 991A>G Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*24 Not Available 99C>T / 991A>G … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*35 Not Available 12662A>G Effect Inferred Poor drug metabolizer. Details
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Flibanserin is combined with 1,2-Benzodiazepine. Abametapir The serum concentration of Flibanserin can be increased when it is combined with Abametapir. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Flibanserin. Acebutolol Flibanserin may decrease the antihypertensive activities of Acebutolol. Aceclofenac The risk or severity of hypertension can be increased when Flibanserin is combined with Aceclofenac. - Food Interactions
- Avoid alcohol. Avoid alcohol. Ingesting alcohol may increase the CNS depressant and hypotensive effects of flibanserin. If you have consumed two drinks, wait two hours before taking flibanserin. Do not take flibanserin if you have consumed more than three drinks.
- Avoid grapefruit products.
- Avoid St. John's Wort.
- Take with or without food. Taking flibanserin with food (especially a high-fat meal) may increase its AUC, Cmax, and Tmax.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Flibanserin hydrochloride 96XTC36K1B 147359-76-0 XGAGFLQFMFCIHZ-UHFFFAOYSA-N - International/Other Brands
- Ectris
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Addyi Tablet, film coated 100 mg/1 Oral Sprout Pharmaceuticals, Inc. 2015-08-18 Not applicable US Addyi Tablet 100 mg Oral Searchlight Pharma Inc 2018-11-13 Not applicable Canada
Categories
- ATC Codes
- G02CX02 — Flibanserin
- Drug Categories
- Agents that produce hypertension
- Antidepressive Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Genito Urinary System and Sex Hormones
- Heterocyclic Compounds, Fused-Ring
- Miscellaneous Central Nervous System Agents
- P-glycoprotein inhibitors
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin 5-HT1 Receptor Agonists
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin 5-HT2A Receptor Antagonists
- Serotonin Agents
- Serotonin Modulators
- Serotonin Receptor Agonists
- Serotonin Receptor Antagonists
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazinanes
- Sub Class
- Piperazines
- Direct Parent
- Phenylpiperazines
- Alternative Parents
- N-arylpiperazines / Trifluoromethylbenzenes / Benzimidazoles / Aniline and substituted anilines / Dialkylarylamines / N-alkylpiperazines / N-substituted imidazoles / Heteroaromatic compounds / Trialkylamines / Ureas show 7 more
- Substituents
- Alkyl fluoride / Alkyl halide / Amine / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Benzimidazole / Dialkylarylamine show 21 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 37JK4STR6Z
- CAS number
- 167933-07-5
- InChI Key
- PPRRDFIXUUSXRA-UHFFFAOYSA-N
- InChI
- InChI=1S/C20H21F3N4O/c21-20(22,23)15-4-3-5-16(14-15)26-11-8-25(9-12-26)10-13-27-18-7-2-1-6-17(18)24-19(27)28/h1-7,14H,8-13H2,(H,24,28)
- IUPAC Name
- 1-(2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)-2,3-dihydro-1H-1,3-benzodiazol-2-one
- SMILES
- FC(F)(F)C1=CC(=CC=C1)N1CCN(CCN2C(=O)NC3=CC=CC=C23)CC1
References
- General References
- Invernizzi RW, Sacchetti G, Parini S, Acconcia S, Samanin R: Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5-HT(1A) receptors. Br J Pharmacol. 2003 Aug;139(7):1281-8. [Article]
- Scandroglio A, Monferini E, Borsini F: Ex vivo binding of flibanserin to serotonin 5-HT1A and 5-HT2A receptors. Pharmacol Res. 2001 Feb;43(2):179-83. [Article]
- Borsini F, Cesana R: Mechanism of action of flibanserin in the learned helplessness paradigm in rats. Eur J Pharmacol. 2001 Dec 14;433(1):81-9. [Article]
- Borsini F, Evans K, Jason K, Rohde F, Alexander B, Pollentier S: Pharmacology of flibanserin. CNS Drug Rev. 2002 Summer;8(2):117-42. [Article]
- Deeks ED: Flibanserin: First Global Approval. Drugs. 2015 Oct;75(15):1815-22. doi: 10.1007/s40265-015-0474-y. [Article]
- Stahl SM: Mechanism of action of flibanserin, a multifunctional serotonin agonist and antagonist (MSAA), in hypoactive sexual desire disorder. CNS Spectr. 2015 Feb;20(1):1-6. doi: 10.1017/S1092852914000832. Epub 2015 Feb 9. [Article]
- FDA Approved Drug Products: ADDYI (flibanserin) tablets [Link]
- External Links
- KEGG Drug
- D02577
- PubChem Compound
- 6918248
- PubChem Substance
- 175426897
- ChemSpider
- 5293454
- BindingDB
- 50476735
- 1665509
- ChEBI
- 90865
- ChEMBL
- CHEMBL231068
- ZINC
- ZINC000052716421
- PharmGKB
- PA166153431
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Flibanserin
- FDA label
- Download (788 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Terminated Treatment Hypoactive Sexual Desire Disorder (HSDD) 1 3 Completed Treatment Sexual Dysfunctions, Psychological 8 3 Terminated Treatment Depression / Sexual Dysfunctions, Psychological 1 3 Terminated Treatment Sexual Dysfunctions, Psychological 3 2 Recruiting Treatment Adenocarcinoma of Prostate 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 100 mg Tablet, film coated Oral 100 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7151103 No 2006-12-19 2023-05-09 US US8227471 No 2012-07-24 2023-05-09 US US7420057 No 2008-09-02 2022-08-01 US US9468639 No 2016-10-18 2022-10-16 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.178 mg/mL ALOGPS logP 3.32 ALOGPS logP 3.83 Chemaxon logS -3.3 ALOGPS pKa (Strongest Acidic) 12.91 Chemaxon pKa (Strongest Basic) 7.03 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 38.82 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 103.65 m3·mol-1 Chemaxon Polarizability 38.69 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9857 Caco-2 permeable - 0.7652 P-glycoprotein substrate Substrate 0.6865 P-glycoprotein inhibitor I Inhibitor 0.8895 P-glycoprotein inhibitor II Inhibitor 0.8741 Renal organic cation transporter Inhibitor 0.6378 CYP450 2C9 substrate Non-substrate 0.7906 CYP450 2D6 substrate Non-substrate 0.5905 CYP450 3A4 substrate Substrate 0.6954 CYP450 1A2 substrate Inhibitor 0.8379 CYP450 2C9 inhibitor Non-inhibitor 0.7028 CYP450 2D6 inhibitor Inhibitor 0.5876 CYP450 2C19 inhibitor Non-inhibitor 0.59 CYP450 3A4 inhibitor Inhibitor 0.7523 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9005 Ames test Non AMES toxic 0.6798 Carcinogenicity Non-carcinogens 0.9354 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.6546 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.6138 hERG inhibition (predictor II) Inhibitor 0.9486
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0019000000-6fe6371d079641bb395a Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0075-0009000000-c925d5782e731dde8e85 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4l-0059000000-848dff230616bb51300d Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00y1-0109000000-00e36939a88eca6efa5b Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-02u3-1921000000-8ef4cee09370096944ab Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-01po-4932000000-8ea4feff344ed82f3dda Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 184.70683 predictedDeepCCS 1.0 (2019) [M+H]+ 187.06483 predictedDeepCCS 1.0 (2019) [M+Na]+ 193.88432 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Serotonin receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
- Gene Name
- HTR1A
- Uniprot ID
- P08908
- Uniprot Name
- 5-hydroxytryptamine receptor 1A
- Molecular Weight
- 46106.335 Da
References
- Invernizzi RW, Sacchetti G, Parini S, Acconcia S, Samanin R: Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5-HT(1A) receptors. Br J Pharmacol. 2003 Aug;139(7):1281-8. [Article]
- Borsini F, Evans K, Jason K, Rohde F, Alexander B, Pollentier S: Pharmacology of flibanserin. CNS Drug Rev. 2002 Summer;8(2):117-42. [Article]
- Deeks ED: Flibanserin: First Global Approval. Drugs. 2015 Oct;75(15):1815-22. doi: 10.1007/s40265-015-0474-y. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Virus receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
- Gene Name
- HTR2A
- Uniprot ID
- P28223
- Uniprot Name
- 5-hydroxytryptamine receptor 2A
- Molecular Weight
- 52602.58 Da
References
- Borsini F, Evans K, Jason K, Rohde F, Alexander B, Pollentier S: Pharmacology of flibanserin. CNS Drug Rev. 2002 Summer;8(2):117-42. [Article]
- Invernizzi RW, Sacchetti G, Parini S, Acconcia S, Samanin R: Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5-HT(1A) receptors. Br J Pharmacol. 2003 Aug;139(7):1281-8. [Article]
- Deeks ED: Flibanserin: First Global Approval. Drugs. 2015 Oct;75(15):1815-22. doi: 10.1007/s40265-015-0474-y. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistAgonist
- General Function
- Sh3 domain binding
- Specific Function
- Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins ...
- Gene Name
- DRD4
- Uniprot ID
- P21917
- Uniprot Name
- D(4) dopamine receptor
- Molecular Weight
- 48359.86 Da
References
- Borsini F, Evans K, Jason K, Rohde F, Alexander B, Pollentier S: Pharmacology of flibanserin. CNS Drug Rev. 2002 Summer;8(2):117-42. [Article]
- Invernizzi RW, Sacchetti G, Parini S, Acconcia S, Samanin R: Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5-HT(1A) receptors. Br J Pharmacol. 2003 Aug;139(7):1281-8. [Article]
- Deeks ED: Flibanserin: First Global Approval. Drugs. 2015 Oct;75(15):1815-22. doi: 10.1007/s40265-015-0474-y. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Deeks ED: Flibanserin: First Global Approval. Drugs. 2015 Oct;75(15):1815-22. doi: 10.1007/s40265-015-0474-y. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
Drug created at October 21, 2007 22:23 / Updated at February 02, 2024 22:53