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

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Flibanserin (DB04908)

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Weight

Average: 390.4021
Monoisotopic: 390.166745929

Chemical Formula

C₂₀H₂₁F₃N₄O

Synonyms

• Flibanserin

External IDs

• BIMT 17
• BIMT 17 BS
• BIMT-17
• BIMT-17-BS

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Pharmacology

Indication

For the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women.

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Treatment of	Hypoactive sexual desire disorder		••••••••••••	•••••••••••••

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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	agonist	Humans
A5-hydroxytryptamine receptor 2A	antagonist	Humans
ADopamine D4 receptor	antagonist agonist	Humans

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

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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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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1,2-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.

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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
Addyi	Tablet	100 mg	Oral	Searchlight Pharma Inc	2018-11-13	Not applicable

Categories

ATC Codes

G02CX02 — Flibanserin

• G02CX — Other gynecologicals
• G02C — OTHER GYNECOLOGICALS
• G02 — OTHER GYNECOLOGICALS
• G — GENITO URINARY SYSTEM AND SEX HORMONES

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 / Azacyclic compounds / Organofluorides / Organic oxides / Hydrocarbon derivatives / Alkyl fluorides / Organooxygen compounds / Organopnictogen compounds

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Substituents

Alkyl fluoride / Alkyl halide / Amine / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Benzimidazole / Dialkylarylamine / Heteroaromatic compound / Hydrocarbon derivative / Imidazole / Monocyclic benzene moiety / N-alkylpiperazine / N-arylpiperazine / N-substituted imidazole / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organofluoride / Organohalogen compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Phenylpiperazine / Tertiary aliphatic amine / Tertiary aliphatic/aromatic amine / Tertiary amine / Trifluoromethylbenzene / Urea

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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

1. 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]
2. 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]
3. 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]
4. 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]
5. Deeks ED: Flibanserin: First Global Approval. Drugs. 2015 Oct;75(15):1815-22. doi: 10.1007/s40265-015-0474-y. [Article]
6. 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]
7. FDA Approved Drug Products: ADDYI (flibanserin) tablets [Link]

External Links

KEGG Drug

D02577

PubChem Compound

6918248

PubChem Substance

175426897

ChemSpider

5293454

BindingDB

50476735

RxNav

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
US8227471	No	2012-07-24	2023-05-09
US7420057	No	2008-09-02	2022-08-01
US9468639	No	2016-10-18	2022-10-16

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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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	predicted	DeepCCS 1.0 (2019)
[M+H]+	187.06483	predicted	DeepCCS 1.0 (2019)
[M+Na]+	193.88432	predicted	DeepCCS 1.0 (2019)

Targets

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Details1. 5-hydroxytryptamine receptor 1A

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

1. 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]
2. 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]
3. Deeks ED: Flibanserin: First Global Approval. Drugs. 2015 Oct;75(15):1815-22. doi: 10.1007/s40265-015-0474-y. [Article]

Details2. 5-hydroxytryptamine receptor 2A

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

1. 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]
2. 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]
3. Deeks ED: Flibanserin: First Global Approval. Drugs. 2015 Oct;75(15):1815-22. doi: 10.1007/s40265-015-0474-y. [Article]

Details3. Dopamine D4 receptor

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

Agonist

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

1. 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]
2. 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]
3. Deeks ED: Flibanserin: First Global Approval. Drugs. 2015 Oct;75(15):1815-22. doi: 10.1007/s40265-015-0474-y. [Article]

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Drug created at October 21, 2007 22:23 / Updated at February 02, 2024 22:53