U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C20H21F3N4O
Molecular Weight 390.4029
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FLIBANSERIN

SMILES

c1ccc2c(c1)nc(n2CCN3CCN(CC3)c4cccc(c4)C(F)(F)F)O

InChI

InChIKey=PPRRDFIXUUSXRA-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C20H21F3N4O
Molecular Weight 390.4029
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB04908

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. 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. Flibanserin is sold under the trade name Addyi and indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) as characterized by low sexual desire that causes marked distress or interpersonal difficulty.

Originator

Curator's Comment:: developed by Sprout Pharmaceuticals https://www.drugs.com/history/addyi.html

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ADDYI

Approved Use

ADDYI is indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to: •A co-existing medical or psychiatric condition, •Problems within the relationship, or •The effects of a medication or other drug substance. Acquired HSDD refers to HSDD that develops in a patient who previously had no problems with sexual desire. Generalized HSDD refers to HSDD that occurs regardless of the type of stimulation, situation or partner. Limitations of Use •ADDYI is not indicated for the treatment of HSDD in postmenopausal women or in men. •ADDYI is not indicated to enhance sexual performance. ADDYI is indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to: •A co-existing medical or psychiatric condition, •Problems within the relationship, or •The effects of a medication or other drug substance. (1) Limitations of Use: •ADDYI is not indicated for the treatment of HSDD in postmenopausal women or in men. (1) •ADDYI is not indicated to enhance sexual performance. (1)

Launch Date

1.43985594E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
419 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLIBANSERIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1543 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLIBANSERIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
11 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLIBANSERIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLIBANSERIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
600 mg single, oral
Dose: 600 mg
Route: oral
Route: single
Dose: 600 mg
Sources:
unknown, 2 yeras
n = 1
Health Status: unknown
Age Group: 2 yeras
Sex: M
Population Size: 1
Sources:
Other AEs: Seizures...
Other AEs:
Seizures (1 patient)
Sources:
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
unhealthy, 36 years (range: 18-56 years)
n = 1543
Health Status: unhealthy
Condition: hypoactive sexual desire disorder
Age Group: 36 years (range: 18-56 years)
Sex: F
Population Size: 1543
Sources:
Disc. AE: Dizziness, Nausea...
AEs leading to
discontinuation/dose reduction:
Dizziness (1.7%)
Nausea (1.2%)
Insomnia (1.1%)
Somnolence (1.1%)
Anxiety (1%)
Sources:
250 mg 1 times / day steady, oral
MTD
Dose: 250 mg, 1 times / day
Route: oral
Route: steady
Dose: 250 mg, 1 times / day
Sources: Page: p. 127
unhealthy
n = 6
Health Status: unhealthy
Sex: F
Population Size: 6
Sources: Page: p. 127
Other AEs: Dizziness, Nausea...
Other AEs:
Dizziness (83%)
Nausea (67%)
Somnolence (83%)
Sources: Page: p. 127
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
alcohol(0.4 g/kg)
Sources:
unhealthy
n = 25
Health Status: unhealthy
Sex: M+F
Population Size: 25
Sources:
Other AEs: Hypotension, Syncope...
20 mg single, intravenous
Dose: 20 mg
Route: intravenous
Route: single
Dose: 20 mg
Sources:
healthy
n = 12
Health Status: healthy
Sex: M
Population Size: 12
Sources:
AEs

AEs

AESignificanceDosePopulation
Seizures 1 patient
600 mg single, oral
Dose: 600 mg
Route: oral
Route: single
Dose: 600 mg
Sources:
unknown, 2 yeras
n = 1
Health Status: unknown
Age Group: 2 yeras
Sex: M
Population Size: 1
Sources:
Anxiety 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
unhealthy, 36 years (range: 18-56 years)
n = 1543
Health Status: unhealthy
Condition: hypoactive sexual desire disorder
Age Group: 36 years (range: 18-56 years)
Sex: F
Population Size: 1543
Sources:
Insomnia 1.1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
unhealthy, 36 years (range: 18-56 years)
n = 1543
Health Status: unhealthy
Condition: hypoactive sexual desire disorder
Age Group: 36 years (range: 18-56 years)
Sex: F
Population Size: 1543
Sources:
Somnolence 1.1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
unhealthy, 36 years (range: 18-56 years)
n = 1543
Health Status: unhealthy
Condition: hypoactive sexual desire disorder
Age Group: 36 years (range: 18-56 years)
Sex: F
Population Size: 1543
Sources:
Nausea 1.2%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
unhealthy, 36 years (range: 18-56 years)
n = 1543
Health Status: unhealthy
Condition: hypoactive sexual desire disorder
Age Group: 36 years (range: 18-56 years)
Sex: F
Population Size: 1543
Sources:
Dizziness 1.7%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
unhealthy, 36 years (range: 18-56 years)
n = 1543
Health Status: unhealthy
Condition: hypoactive sexual desire disorder
Age Group: 36 years (range: 18-56 years)
Sex: F
Population Size: 1543
Sources:
Nausea 67%
250 mg 1 times / day steady, oral
MTD
Dose: 250 mg, 1 times / day
Route: oral
Route: steady
Dose: 250 mg, 1 times / day
Sources: Page: p. 127
unhealthy
n = 6
Health Status: unhealthy
Sex: F
Population Size: 6
Sources: Page: p. 127
Dizziness 83%
250 mg 1 times / day steady, oral
MTD
Dose: 250 mg, 1 times / day
Route: oral
Route: steady
Dose: 250 mg, 1 times / day
Sources: Page: p. 127
unhealthy
n = 6
Health Status: unhealthy
Sex: F
Population Size: 6
Sources: Page: p. 127
Somnolence 83%
250 mg 1 times / day steady, oral
MTD
Dose: 250 mg, 1 times / day
Route: oral
Route: steady
Dose: 250 mg, 1 times / day
Sources: Page: p. 127
unhealthy
n = 6
Health Status: unhealthy
Sex: F
Population Size: 6
Sources: Page: p. 127
Syncope
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
alcohol(0.4 g/kg)
Sources:
unhealthy
n = 25
Health Status: unhealthy
Sex: M+F
Population Size: 25
Sources:
Hypotension severe
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
alcohol(0.4 g/kg)
Sources:
unhealthy
n = 25
Health Status: unhealthy
Sex: M+F
Population Size: 25
Sources:
Overview

OverviewOther

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
yes [Ki 6.4 uM]
yes [Ki 7.5 uM]
yes
yes (co-administration study)
Comment: Digoxin exposure increased by 46%, 62% and 96% for Cmax, AUC0-t, and AUC0-inf, respectively, following multiple doses of flibanserin 100 mg co-administered with a single dose of digoxin 0.5 mg. A 96% increase in digoxin AUC suggests flibanserin is a P-gp inhibitor.
Page: 71.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
likely
major
yes (co-administration study)
Comment: In a pharmacokinetic drug interaction study of 50 mg flibanserin and 400 mg ketoconazole, a strong CYP3A4 inhibitor, syncope occurred in 1/24 (4%) healthy subjects treated with concomitant flibanserin and ketoconazole, 1/24 (4%) receiving flibanserin alone, and no subjects receiving ketoconazole alone. In this study, the concomitant use of flibanserin and ketoconazole increased flibanserin exposure 4.5-fold
Page: 44.0
poor
poor
poor
poor
no (co-administration study)
Comment: A study comparing flibanserin exposure in CYP2C9 poor metabolizers to CYP2C9 extensive metabolizers was conducted in lieu of a drug interaction study with ADDYI and a strong CYP2C9 inhibitor. In 8 women who were poor metabolizers of CYP2C9, Cmax and AUC0-inf of flibanserin 100 mg once daily decreased 23% and 18%, compared to exposures among 8 extensive metabolizers of CYP2C9.
Page: 44.0
poor
no (co-administration study)
Comment: Paroxetine is a strong CYP2D6 inhibitor. In a study of 19 healthy male and female subjects, flibanserin exposure decreased by approximately 4% when flibanserin 50 mg twice daily was given with paroxetine compared to flibanserin alone. Paroxetine was dosed at 20 mg once daily for 3 days followed by 40 mg once daily for 7 days.
Page: 44.0
yes
yes
yes
yes (pharmacogenomic study)
Comment: In a pharmacogenomic study of 100 mg ADDYI in subjects who were poor or extensive CYP2C19 metabolizers, syncope occurred in 1/9 (11%) subjects who were CYP2C19 poor metabolizers (this subject had a 3.2 fold higher flibanserin exposure compared to CYP2C19 extensive metabolizers) compared to no such adverse reactions in subjects who were CYP2C19 extensive metabolizers
Page: 44.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Anti-anhedonic actions of the novel serotonergic agent flibanserin, a potential rapidly-acting antidepressant.
1997 Dec 11
Further characterisation of potential antidepressant action of flibanserin.
2001 Dec
Mechanism of action of flibanserin in the learned helplessness paradigm in rats.
2001 Dec 14
Ex vivo binding of flibanserin to serotonin 5-HT1A and 5-HT2A receptors.
2001 Feb
Lack of interaction between flibanserin and antidepressants in inducing serotonergic syndrome in rats.
2001 Mar
Region-dependent effects of flibanserin and buspirone on adenylyl cyclase activity in the human brain.
2002 Jun
Association of the C(-1019)G 5-HT1A functional promoter polymorphism with antidepressant response.
2004 Dec
Redistribution of the water channel protein aquaporin-4 and the K+ channel protein Kir4.1 differs in low- and high-grade human brain tumors.
2005 Apr
Agonist and antagonist properties of antipsychotics at human dopamine D4.4 receptors: G-protein activation and K+ channel modulation in transfected cells.
2008 May
Gateways to clinical trials.
2009 May
A new strategy for antidepressant prescription.
2010
Modifying 5-HT1A Receptor Gene Expression as a New Target for Antidepressant Therapy.
2010
Dysfunctional women remain unsexed.
2010 Aug
Management of hypoactive sexual desire disorder in women: current and emerging therapies.
2010 Aug 9
[Normality of the female libido? (2)].
2010 Jul 14
Drug for low sexual desire carries significant harms, FDA advisers find.
2010 Jul 7
Flibanserin, a drug intended for treatment of hypoactive sexual desire disorder in pre-menopausal women, affects spontaneous motor activity and brain neurochemistry in female rats.
2010 Jun
[Normality of the female libido (1)].
2010 Jun 30
Involvement of serotonin receptor subtypes in the antidepressant-like effect of TRIM in the rat forced swimming test.
2010 May
Acute and repeated flibanserin administration in female rats modulates monoamines differentially across brain areas: a microdialysis study.
2010 May
FDA advisers to assess drug for low sexual desire in women.
2010 May 25
Consultation corner. The latest on female sexual health.
2010 Nov
Flibanserin: initial evidence of efficacy on sexual dysfunction, in patients with major depressive disorder.
2010 Oct
Boehringer Ingelheim withdraws libido drug for women.
2010 Oct 12
[The abandonment of the development of flibanserin].
2010 Oct 27
Do drugs have a role in turning indifference into passion?
2010 Oct 5
Flibanserin: a potential treatment for Hypoactive Sexual Desire Disorder in premenopausal women.
2010 Sep
Predicting in vivo absorption behavior of oral modified release dosage forms containing pH-dependent poorly soluble drugs using a novel pH-adjusted biphasic in vitro dissolution test.
2010 Sep
Mechanism of action of flibanserin, a multifunctional serotonin agonist and antagonist (MSAA), in hypoactive sexual desire disorder.
2015 Feb
Flibanserin: First Global Approval.
2015 Oct
Patents

Sample Use Guides

Recommended dosage is 100 mg taken once daily at bedtime, discontinue treatment after 8 weeks if no improvement
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment:: Flibanserin behaves as a 5-HT1A agonist in the cortex and hippo-campus of human and rat brain
The concentration that reduces forskolin-induced cAMP formation by 50% in human hippocampus tissue was 4 nM.
Substance Class Chemical
Created
by admin
on Sat Jun 26 05:37:00 UTC 2021
Edited
by admin
on Sat Jun 26 05:37:00 UTC 2021
Record UNII
37JK4STR6Z
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FLIBANSERIN
DASH   INN   MART.   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
1,3-DIHYDRO-1-(2-(4-(3-(TRIFLUOROMETHYL)PHENYL)-1-PIPERAZINYL)ETHYL)-2H-BENZIMIDAZOL-2-ONE
Systematic Name English
BIMT 17 BS
Code English
1-(2-(4-(.ALPHA.,.ALPHA.,.ALPHA.-TRIFLUORO-M-TOLYL)-1-PIPERAZINYL)ETHYL)-2-BENZIMIDAZOLINONE
Systematic Name English
BIMT-17-BS
Code English
BIMT 17
Code English
ADDYI
Brand Name English
FLIBANSERIN [INN]
Common Name English
FLIBANSERIN [MART.]
Common Name English
FLIBANSERIN [USAN]
Common Name English
BIMT-17
Code English
FLIBANSERIN [ORANGE BOOK]
Common Name English
ECTRIS
Brand Name English
FLIBANSERIN [WHO-DD]
Common Name English
FLIBANSERIN [MI]
Common Name English
Classification Tree Code System Code
WHO-ATC G02CX02
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
NCI_THESAURUS C66885
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
Code System Code Type Description
MERCK INDEX
M5402
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
PRIMARY Merck Index
NCI_THESAURUS
C80769
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
PRIMARY
IUPHAR
8182
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
PRIMARY
ChEMBL
CHEMBL231068
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
PRIMARY
RXCUI
1665509
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
PRIMARY RxNorm
DRUG CENTRAL
5022
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
PRIMARY
FDA UNII
37JK4STR6Z
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
PRIMARY
CAS
167933-07-5
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
PRIMARY
MESH
C098107
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
PRIMARY
DRUG BANK
DB04908
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
PRIMARY
NDF-RT
N0000185503
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
PRIMARY P-Glycoprotein Inhibitors [MoA]
PUBCHEM
6918248
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
PRIMARY
INN
7512
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
PRIMARY
WIKIPEDIA
FLIBANSERIN
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
PRIMARY
EPA CompTox
167933-07-5
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
PRIMARY
EVMPD
SUB07644MIG
Created by admin on Sat Jun 26 05:37:00 UTC 2021 , Edited by admin on Sat Jun 26 05:37:00 UTC 2021
PRIMARY
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SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC SINGLE DOSE

ORAL ADMINISTRATION

ORAL BIOAVAILABILITY PHARMACOKINETIC SINGLE DOSE

ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC SINGLE DOSE

ORAL ADMINISTRATION