Details
Stereochemistry | ACHIRAL |
Molecular Formula | C20H21F3N4O.ClH |
Molecular Weight | 426.863 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.FC(F)(F)C1=CC=CC(=C1)N2CCN(CCN3C(=O)NC4=C3C=CC=C4)CC2
InChI
InChIKey=XGAGFLQFMFCIHZ-UHFFFAOYSA-N
InChI=1S/C20H21F3N4O.ClH/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);1H
DescriptionSources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022526lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/12177684Curator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB04908
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022526lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/12177684
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.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
7.31 null [pKi] | |||
4.0 nM [EC50] | |||
115.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ADDYI Approved UseADDYI 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 Date2015 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse events |
---|---|---|
600 mg single, oral |
unknown, 2 yeras n = 1 Health Status: unknown Age Group: 2 yeras Sex: M Population Size: 1 Sources: |
Other AEs: Seizures... |
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%) Sources: Nausea (1.2%) Insomnia (1.1%) Somnolence (1.1%) Anxiety (1%) |
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%) Sources: Page: p. 127Nausea (67%) Somnolence (83%) |
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... Other AEs: Hypotension (severe) Sources: Syncope |
20 mg single, intravenous Dose: 20 mg Route: intravenous Route: single Dose: 20 mg Sources: |
healthy n = 12 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Seizures | 1 patient | 600 mg single, oral |
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=254 Page: 254.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=187 Page: 187.0 |
yes [Ki 6.4 uM] | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=187 Page: 187.0 |
yes [Ki 7.5 uM] | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=71 Page: 71.0 |
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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=71 Page: 71.0 |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=117 Page: 117.0 |
likely | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=44 Page: 44.0 |
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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=44 Page: 44.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=44 Page: 44.0 |
poor | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=44 Page: 44.0 |
poor | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=44 Page: 44.0 |
poor | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=44 Page: 44.0 |
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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=44 Page: 44.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=44 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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=44 Page: 44.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=167 Page: 167.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=167 Page: 167.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=44 Page: 44.0 |
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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000ClinPharmR.pdf#page=44 Page: 44.0 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000PharmR.pdf#page=231 Page: 231.0 |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
|
Region-dependent effects of flibanserin and buspirone on adenylyl cyclase activity in the human brain. | 2002 Jun |
|
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 |
|
Management of hypoactive sexual desire disorder in women: current and emerging therapies. | 2010 Aug 9 |
|
Involvement of serotonin receptor subtypes in the antidepressant-like effect of TRIM in the rat forced swimming test. | 2010 May |
|
Boehringer Ingelheim withdraws libido drug for women. | 2010 Oct 12 |
|
Flibanserin: a potential treatment for Hypoactive Sexual Desire Disorder in premenopausal women. | 2010 Sep |
|
[When women complain about lacking libido. The problem with the desire]. | 2010 Sep 2 |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12177684
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.
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DBSALT001321
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147359-76-0
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96XTC36K1B
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m5402
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9845393
Created by
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PARENT (SALT/SOLVATE)
SUBSTANCE RECORD