Identification

Name
Fenfluramine
Accession Number
DB00574
Description

Dravet syndrome is a pediatric encephalopathy that typically manifests within the first year of life following exposure to elevated temperatures. It is characterized by recurrent pharmacoresistant seizures, which increase in frequency and severity with disease progression. Concomitantly with these seizures, patients typically display delayed development and neurocognitive impairment.6,9,10,11 Fenfluramine is a serotonergic phenethylamine originally used as an appetite suppressant until concerns regarding cardiotoxicity in obese patients lead to its withdrawal from the market in 1997.6,12,13 Through its ability to modulate neurotransmission, fenfluramine has reemerged as an effective therapy against pharmacoresistant seizures, such as those involved in Dravet syndrome.3,5,8

Fenfluramine was granted initial FDA approval in 1973 prior to its withdrawal; it was granted a new FDA approval on June 25, 2020, for treatment of Dravet syndrome patients through the restricted FINTEPLA REMS program. It is currently sold under the name FINTEPLA® by Zogenix INC.16

Type
Small Molecule
Groups
Approved, Illicit, Investigational, Withdrawn
Structure
Thumb
Weight
Average: 231.2573
Monoisotopic: 231.123484132
Chemical Formula
C12H16F3N
Synonyms
  • (±)-fenfluramine
  • 1-(m-trifluoromethyl-phenyl)-2-ethylaminopropane
  • DL-Fenfluramine
  • Fenfluramina
  • Fenfluramine
  • Fenfluraminum
External IDs
  • DEA No. 1670
  • S 768

Pharmacology

Indication

Fenfluramine is indicated for the treatment of seizures in Dravet syndrome patients aged two years and older.16

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Fenfluramine increases extracellular serotonin levels, and also acts as both a serotonergic 5-HT2 receptor agonist and σ1 receptor antagonist. These activities, through an incompletely understood mechanism, lead to anti-epileptiform activity and therapeutic benefit.1,2,3,4,5,6,7,8,16 This modulation has other effects such as decreased appetite, weight loss, sedation, lethargy, increased blood pressure, and mood alteration including possible suicidal ideation. There is a risk of glaucoma and potentially fatal serotonin syndrome. Fenfluramine should be gradually withdrawn following treatment alteration or cessation.16

Mechanism of action

Dravet syndrome is a complex pediatric encephalopathy characterized by recurrent pharmacoresistant seizures of variable type, delayed development, and in many cases, impairment in speech, language, gait, and other neurocognitive functions.6,9,10,11 Despite substantial variation in presentation and severity, roughly 80% of patients with Dravet syndrome have mutations in the SCN1A gene, which encodes the alpha subunit of a voltage-gated sodium channel (Nav1.1).2,3,5,8,9,11 This channel is predominantly localized in inhibitory GABAergic interneurons as well as in excitatory pyramidal neurons; it is thought that dysfunction of neurotransmission regulation results in the seizures and other corresponding symptoms of Dravet syndrome.8,9

Various in vitro and in vivo studies have demonstrated that fenfluramine is capable of acting as an agonist of multiple serotonin receptors including 5-HT1A, 5-HT1D, 5-HT2A, 5-HT2B, and 5-HT2C, as well as a σ1 receptor antagonist.1,2,3,4,5,6,7,8,16 This is at least partly because fenfluramine, as well as its active metabolite norfenfluramine, can act on sodium-dependent serotonin transporters (SERTs) to reverse transport direction and thereby increase extracellular serotonin levels.14,15 However, work in animal models of Dravet syndrome suggest that only the modulation of 5-HT1D, 5-HT2C, σ1, and possibly 5-HT2A receptors of fenfluramine result in the anti-epileptiform activity.3,5,8 Interestingly, 5-HT2B receptor agonism, which had previously been associated with cardiac valvulopathy,12,13 is not anticipated to have any therapeutic value in Dravet syndrome.8

Although the exact mechanism by which stimulation/inhibition of various receptors leads to the observed therapeutic benefit is unclear, it is hypothesized to be two-fold. Stimulation of 5-HT1D and 5-HT2C may result in increased GABAergic neurotransmission, while σ1 receptor antagonism may help to modulate responses to N-methyl-D-aspartate (NMDA).8

TargetActionsOrganism
ASodium-dependent serotonin transporter
substrate
inhibitor
Humans
A5-hydroxytryptamine receptor 1D
agonist
Humans
A5-hydroxytryptamine receptor 2C
agonist
Humans
ASigma non-opioid intracellular receptor 1
antagonist
Humans
U5-hydroxytryptamine receptor 2A
agonist
Humans
N5-hydroxytryptamine receptor 2B
agonist
Humans
N5-hydroxytryptamine receptor 1A
agonist
Humans
Absorption

Fenfluramine has a steady-state Tmax of between four and five hours and an absolute bioavailability of approximately 68-74%. Fenfluramine administered to pediatric patients at 0.7 mg/kg/day up to 26 mg resulted in a mean Cmax of 68.0 ng/mL with a coefficient of variation of 41%; similarly the AUC0-24 was 1390 (44%) ng*h/mL.16

Volume of distribution

Fenfluramine has an apparent volume of distribution of 11.9 L/kg with a coefficient of variation of 16.5% following oral administration in healthy subjects.16

Protein binding

Fenfluramine is 50% bound to plasma proteins independent of plasma drug concentration.16

Metabolism

Fenfluramine is metabolized primarily in the liver by CYP1A2, CYP2B6, CYP2D6, CYP2C9, CYP2C19, and CYP3A4/5 to yield the major active metabolite norfenfluramine and several other minor inactive metabolites.16

Hover over products below to view reaction partners

Route of elimination

Over 90% of fenfluramine is excreted in urine and less than 5% in feces; unchanged fenfluramine and the major active metabolite norfenfluramine account for less than 25% of the recovered amount.16

Half-life

Fenfluramine has an elimination half-life of 20 hours in healthy subjects.16

Clearance

Fenfluramine has a mean clearance of 24.8 L/h with a coefficient of variation of 29% in healthy subjects.16

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Overdosage of fenfluramine has been reported; in overdose cases, symptoms include agitation, anxiety, restlessness, twitching, tremors/muscle spasms, flushing, tachycardia, mydriasis, increased muscle tone, respiratory distress/failure, seizure, and coma. Some overdosage cases proved fatal, and in most fatal cases, patients experienced seizures, coma, and cardiorespiratory arrest.16

There is currently no standard practice for managing fenfluramine overdose. Symptomatic management, including ensuring proper ventilation and monitoring of both cardiac and respiratory functions is recommended.16

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
AcebutololThe metabolism of Acebutolol can be decreased when combined with Fenfluramine.
AcenocoumarolThe risk or severity of adverse effects can be increased when Fenfluramine is combined with Acenocoumarol.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Fenfluramine.
AcetazolamideThe risk or severity of adverse effects can be increased when Fenfluramine is combined with Acetazolamide.
AcetophenazineThe risk or severity of adverse effects can be increased when Fenfluramine is combined with Acetophenazine.
AclidiniumFenfluramine may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AgomelatineThe risk or severity of adverse effects can be increased when Fenfluramine is combined with Agomelatine.
AlfentanilThe risk or severity of serotonin syndrome can be increased when Fenfluramine is combined with Alfentanil.
AlimemazineThe risk or severity of adverse effects can be increased when Fenfluramine is combined with Alimemazine.
AlmotriptanThe risk or severity of serotonin syndrome can be increased when Fenfluramine is combined with Almotriptan.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
  • Take with or without food. The absorption is unaffected by food.

Products

Product Ingredients
IngredientUNIICASInChI Key
Fenfluramine hydrochloride3KC089243P404-82-0ZXKXJHAOUFHNAS-UHFFFAOYSA-N
International/Other Brands
Adifax / Obedrex / Ponderax / Ponderax PA / Pondimin / Rotondin
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FinteplaSolution2.2 mg/1mLOralZogenix, Inc.2020-06-26Not applicableUs
Pondimin Tab 20mgTabletOralAyerst Laboratories1991-12-311997-08-15Canada
Pondimin Tab 20mgTabletOralWyeth Ayerst Canada Inc.1996-09-231998-08-13Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more

Categories

ATC Codes
A08AA02 — Fenfluramine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenethylamines
Direct Parent
Amphetamines and derivatives
Alternative Parents
Trifluoromethylbenzenes / Phenylpropanes / Aralkylamines / Dialkylamines / Organopnictogen compounds / Organofluorides / Hydrocarbon derivatives / Alkyl fluorides
Substituents
Alkyl fluoride / Alkyl halide / Amine / Amphetamine or derivatives / Aralkylamine / Aromatic homomonocyclic compound / Hydrocarbon derivative / Organic nitrogen compound / Organofluoride / Organohalogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
secondary amino compound, (trifluoromethyl)benzenes (CHEBI:5000)

Chemical Identifiers

UNII
2DS058H2CF
CAS number
458-24-2
InChI Key
DBGIVFWFUFKIQN-UHFFFAOYSA-N
InChI
InChI=1S/C12H16F3N/c1-3-16-9(2)7-10-5-4-6-11(8-10)12(13,14)15/h4-6,8-9,16H,3,7H2,1-2H3
IUPAC Name
ethyl({1-[3-(trifluoromethyl)phenyl]propan-2-yl})amine
SMILES
CCNC(C)CC1=CC=CC(=C1)C(F)(F)F

References

Synthesis Reference

Vincenzo Cannata, Barbara Galbiati, Angelo Spreafico, "Process for manufacturing 1-(3-trifluoromethyl)-phenyl-propan-2-one intermediate in the synthesis of the fenfluramine." U.S. Patent US5811586, issued August, 1965.

US5811586
General References
  1. Fuller RW, Snoddy HD, Robertson DW: Mechanisms of effects of d-fenfluramine on brain serotonin metabolism in rats: uptake inhibition versus release. Pharmacol Biochem Behav. 1988 Jul;30(3):715-21. doi: 10.1016/0091-3057(88)90089-5. [PubMed:2463643]
  2. Griffin A, Hamling KR, Knupp K, Hong S, Lee LP, Baraban SC: Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome. Brain. 2017 Mar 1;140(3):669-683. doi: 10.1093/brain/aww342. [PubMed:28073790]
  3. Martin P, de Witte PAM, Maurice T, Gammaitoni A, Farfel G, Galer B: Fenfluramine acts as a positive modulator of sigma-1 receptors. Epilepsy Behav. 2020 Apr;105:106989. doi: 10.1016/j.yebeh.2020.106989. Epub 2020 Mar 10. [PubMed:32169824]
  4. Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ: Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells. Br J Pharmacol. 1999 Sep;128(1):13-20. [PubMed:10498829]
  5. Rodriguez-Munoz M, Sanchez-Blazquez P, Garzon J: Fenfluramine diminishes NMDA receptor-mediated seizures via its mixed activity at serotonin 5HT2A and type 1 sigma receptors. Oncotarget. 2018 May 4;9(34):23373-23389. doi: 10.18632/oncotarget.25169. eCollection 2018 May 4. [PubMed:29805740]
  6. Schoonjans AS, Ceulemans B: An Old Drug for a New Indication: Repurposing Fenfluramine From an Anorexigen to an Antiepileptic Drug. Clin Pharmacol Ther. 2019 Nov;106(5):929-932. doi: 10.1002/cpt.1469. Epub 2019 May 22. [PubMed:31116409]
  7. Sourbron J, Schneider H, Kecskes A, Liu Y, Buening EM, Lagae L, Smolders I, de Witte P: Serotonergic Modulation as Effective Treatment for Dravet Syndrome in a Zebrafish Mutant Model. ACS Chem Neurosci. 2016 May 18;7(5):588-98. doi: 10.1021/acschemneuro.5b00342. Epub 2016 Feb 17. [PubMed:26822114]
  8. Sourbron J, Smolders I, de Witte P, Lagae L: Pharmacological Analysis of the Anti-epileptic Mechanisms of Fenfluramine in scn1a Mutant Zebrafish. Front Pharmacol. 2017 Apr 6;8:191. doi: 10.3389/fphar.2017.00191. eCollection 2017. [PubMed:28428755]
  9. Gataullina S, Dulac O: From genotype to phenotype in Dravet disease. Seizure. 2017 Jan;44:58-64. doi: 10.1016/j.seizure.2016.10.014. Epub 2016 Oct 21. [PubMed:27817982]
  10. Gonzalez-Giraldo E, Sullivan JE: Advances in the Treatment of Drug-Resistant Pediatric Epilepsy. Semin Neurol. 2020 Apr;40(2):257-262. doi: 10.1055/s-0040-1702941. Epub 2020 Mar 17. [PubMed:32185791]
  11. Wheless JW, Fulton SP, Mudigoudar BD: Dravet Syndrome: A Review of Current Management. Pediatr Neurol. 2020 Jun;107:28-40. doi: 10.1016/j.pediatrneurol.2020.01.005. Epub 2020 Jan 31. [PubMed:32165031]
  12. Connolly HM, Crary JL, McGoon MD, Hensrud DD, Edwards BS, Edwards WD, Schaff HV: Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med. 1997 Aug 28;337(9):581-8. doi: 10.1056/NEJM199708283370901. [PubMed:9271479]
  13. Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL: Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation. 2000 Dec 5;102(23):2836-41. [PubMed:11104741]
  14. Rothman RB, Baumann MH, Blough BE, Jacobson AE, Rice KC, Partilla JS: Evidence for noncompetitive modulation of substrate-induced serotonin release. Synapse. 2010 Nov;64(11):862-9. doi: 10.1002/syn.20804. [PubMed:20842720]
  15. Baumann MH, Bulling S, Benaderet TS, Saha K, Ayestas MA, Partilla JS, Ali SF, Stockner T, Rothman RB, Sandtner W, Sitte HH: Evidence for a role of transporter-mediated currents in the depletion of brain serotonin induced by serotonin transporter substrates. Neuropsychopharmacology. 2014 May;39(6):1355-65. doi: 10.1038/npp.2013.331. Epub 2013 Nov 28. [PubMed:24287719]
  16. FDA Approved Drug Products: Fintepla (fenfluramine) oral solution [Link]
  17. PubChem: fenfluramine [Link]
  18. MSDS: fenfluramine [Link]
KEGG Drug
D07945
KEGG Compound
C06996
PubChem Compound
3337
PubChem Substance
46506096
ChemSpider
3220
BindingDB
84738
RxNav
4328
ChEBI
5000
ChEMBL
CHEMBL87493
Therapeutic Targets Database
DAP001478
PharmGKB
PA449592
RxList
RxList Drug Page
Wikipedia
Fenfluramine
MSDS
Download (25.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentDravet Syndrome / Seizures Disorders1
3Active Not RecruitingTreatmentPhotosensitive Epilepsy1
3CompletedTreatmentDravet Syndrome1
3Enrolling by InvitationTreatmentDravet Syndrome2
3Enrolling by InvitationTreatmentDravet Syndrome / Epileptic Encephalopathy / Lennox Gastaut Syndrome / Lennox-Gastaut Syndrome (LGS)1
3RecruitingTreatmentDravet Syndrome1
3RecruitingTreatmentLennox Gastaut Syndrome / Lennox-Gastaut Syndrome (LGS)1
2Active Not RecruitingTreatmentEpilepsies / Lennox Gastaut Syndrome / Lennox-Gastaut Syndrome (LGS)1
2CompletedTreatmentBMI >30 kg/m2 / Heart Diseases / Vascular Diseases1
2Not Yet RecruitingTreatmentInfantile Spasms (IS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
SolutionOral2.2 mg/1mL
TabletOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)160-170L14632
boiling point (°C)108-112L14632
water solubility412 mg/LL14632
pKa9.92L14632
Predicted Properties
PropertyValueSource
Water Solubility0.0215 mg/mLALOGPS
logP3.3ALOGPS
logP3.47ChemAxon
logS-4ALOGPS
pKa (Strongest Basic)10.22ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area12.03 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity59.2 m3·mol-1ChemAxon
Polarizability22.69 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9868
Caco-2 permeable+0.7004
P-glycoprotein substrateNon-substrate0.5138
P-glycoprotein inhibitor INon-inhibitor0.5934
P-glycoprotein inhibitor IINon-inhibitor0.8383
Renal organic cation transporterNon-inhibitor0.7404
CYP450 2C9 substrateNon-substrate0.8506
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateNon-substrate0.6781
CYP450 1A2 substrateInhibitor0.8859
CYP450 2C9 inhibitorNon-inhibitor0.8616
CYP450 2D6 inhibitorInhibitor0.7253
CYP450 2C19 inhibitorNon-inhibitor0.5205
CYP450 3A4 inhibitorNon-inhibitor0.5219
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6657
Ames testNon AMES toxic0.8808
CarcinogenicityNon-carcinogens0.6397
BiodegradationNot ready biodegradable0.984
Rat acute toxicity3.1255 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9666
hERG inhibition (predictor II)Inhibitor0.7811
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0090000000-41a095f72665e3a6fc34
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0910000000-481b943f32db11f34ee9
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0900000000-b47283685814bef28517
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0900000000-68de81754e901e800d97
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0900000000-051ff0ad0ba0c9f76270
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-014i-0290000000-a4eef1b513aee06fe04c
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00kb-2930000000-e89db6ca285f5e38a85e
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4j-5900000000-d43b57acff766553a26a
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4i-9600000000-b49ac50c8a44403f71f6
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0aor-9400000000-98167d6254e10b1cb5fe
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-0a4r-0900000000-8fa48db488adb62ea334
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-053r-0970000000-f9a49d7622ec3ba9a1d4
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0900000000-ab20d5fae96b357efb96
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0900000000-486062095dc4b5f9673d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0900000000-f339087f5b3e001e72e8
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0900000000-7d7a0ce1b53c5f8aca3e

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Substrate
Inhibitor
Curator comments
Fenfluramine, as well as its active metabolite norfenfluramine, are substrates for the SERT transporter. Through an incompletely understood mechanism, potentially involving ion exchange, the transport of these compounds results in a reversal of SERT transport and an increase in extracellular 5-HT.
General Function
Serotonin:sodium symporter activity
Specific Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. Rothman RB, Zolkowska D, Baumann MH: Serotonin (5-HT) transporter ligands affect plasma 5-HT in rats. Ann N Y Acad Sci. 2008 Oct;1139:268-84. doi: 10.1196/annals.1432.042. [PubMed:18991872]
  2. Xie T, Tong L, McLane MW, Hatzidimitriou G, Yuan J, McCann U, Ricaurte G: Loss of serotonin transporter protein after MDMA and other ring-substituted amphetamines. Neuropsychopharmacology. 2006 Dec;31(12):2639-51. Epub 2006 Jan 25. [PubMed:16452989]
  3. Johnson GJ, Leis LA, Dunlop PC, Weir EK: The effect of the anorectic agent, d-fenfluramine, and its primary metabolite, d-norfenfluramine, on intact human platelet serotonin uptake and efflux. J Thromb Haemost. 2003 Dec;1(12):2663-8. [PubMed:14675103]
  4. Rothman RB, Jayanthi S, Wang X, Dersch CM, Cadet JL, Prisinzano T, Rice KC, Baumann MH: High-dose fenfluramine administration decreases serotonin transporter binding, but not serotonin transporter protein levels, in rat forebrain. Synapse. 2003 Dec 1;50(3):233-9. [PubMed:14515341]
  5. Rothman RB, Baumann MH, Blough BE, Jacobson AE, Rice KC, Partilla JS: Evidence for noncompetitive modulation of substrate-induced serotonin release. Synapse. 2010 Nov;64(11):862-9. doi: 10.1002/syn.20804. [PubMed:20842720]
  6. Baumann MH, Bulling S, Benaderet TS, Saha K, Ayestas MA, Partilla JS, Ali SF, Stockner T, Rothman RB, Sandtner W, Sitte HH: Evidence for a role of transporter-mediated currents in the depletion of brain serotonin induced by serotonin transporter substrates. Neuropsychopharmacology. 2014 May;39(6):1355-65. doi: 10.1038/npp.2013.331. Epub 2013 Nov 28. [PubMed:24287719]
  7. FDA Approved Drug Products: Fintepla (fenfluramine) oral solution [Link]
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 ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1D
Uniprot ID
P28221
Uniprot Name
5-hydroxytryptamine receptor 1D
Molecular Weight
41906.38 Da
References
  1. Schoonjans AS, Ceulemans B: An Old Drug for a New Indication: Repurposing Fenfluramine From an Anorexigen to an Antiepileptic Drug. Clin Pharmacol Ther. 2019 Nov;106(5):929-932. doi: 10.1002/cpt.1469. Epub 2019 May 22. [PubMed:31116409]
  2. Sourbron J, Schneider H, Kecskes A, Liu Y, Buening EM, Lagae L, Smolders I, de Witte P: Serotonergic Modulation as Effective Treatment for Dravet Syndrome in a Zebrafish Mutant Model. ACS Chem Neurosci. 2016 May 18;7(5):588-98. doi: 10.1021/acschemneuro.5b00342. Epub 2016 Feb 17. [PubMed:26822114]
  3. Sourbron J, Smolders I, de Witte P, Lagae L: Pharmacological Analysis of the Anti-epileptic Mechanisms of Fenfluramine in scn1a Mutant Zebrafish. Front Pharmacol. 2017 Apr 6;8:191. doi: 10.3389/fphar.2017.00191. eCollection 2017. [PubMed:28428755]
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, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. Fitzgerald LW, Burn TC, Brown BS, Patterson JP, Corjay MH, Valentine PA, Sun JH, Link JR, Abbaszade I, Hollis JM, Largent BL, Hartig PR, Hollis GF, Meunier PC, Robichaud AJ, Robertson DW: Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine. Mol Pharmacol. 2000 Jan;57(1):75-81. [PubMed:10617681]
  2. McCreary AC, Filip M, Cunningham KA: Discriminative stimulus properties of (+/-)-fenfluramine: the role of 5-HT2 receptor subtypes. Behav Neurosci. 2003 Apr;117(2):212-21. [PubMed:12708517]
  3. Schuhler S, Clark A, Joseph W, Patel A, Lehnen K, Stratford E, Horan TL, Fone KC, Ebling FJ: Involvement of 5-HT receptors in the regulation of food intake in Siberian hamsters. J Neuroendocrinol. 2005 May;17(5):276-85. [PubMed:15869562]
  4. Miller KJ: Serotonin 5-ht2c receptor agonists: potential for the treatment of obesity. Mol Interv. 2005 Oct;5(5):282-91. [PubMed:16249524]
  5. Nonogaki K, Nozue K, Oka Y: Hyperphagia alters expression of hypothalamic 5-HT2C and 5-HT1B receptor genes and plasma des-acyl ghrelin levels in Ay mice. Endocrinology. 2006 Dec;147(12):5893-900. Epub 2006 Sep 14. [PubMed:16973729]
  6. Martin P, de Witte PAM, Maurice T, Gammaitoni A, Farfel G, Galer B: Fenfluramine acts as a positive modulator of sigma-1 receptors. Epilepsy Behav. 2020 Apr;105:106989. doi: 10.1016/j.yebeh.2020.106989. Epub 2020 Mar 10. [PubMed:32169824]
  7. Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ: Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells. Br J Pharmacol. 1999 Sep;128(1):13-20. [PubMed:10498829]
  8. Rodriguez-Munoz M, Sanchez-Blazquez P, Garzon J: Fenfluramine diminishes NMDA receptor-mediated seizures via its mixed activity at serotonin 5HT2A and type 1 sigma receptors. Oncotarget. 2018 May 4;9(34):23373-23389. doi: 10.18632/oncotarget.25169. eCollection 2018 May 4. [PubMed:29805740]
  9. Schoonjans AS, Ceulemans B: An Old Drug for a New Indication: Repurposing Fenfluramine From an Anorexigen to an Antiepileptic Drug. Clin Pharmacol Ther. 2019 Nov;106(5):929-932. doi: 10.1002/cpt.1469. Epub 2019 May 22. [PubMed:31116409]
  10. Sourbron J, Schneider H, Kecskes A, Liu Y, Buening EM, Lagae L, Smolders I, de Witte P: Serotonergic Modulation as Effective Treatment for Dravet Syndrome in a Zebrafish Mutant Model. ACS Chem Neurosci. 2016 May 18;7(5):588-98. doi: 10.1021/acschemneuro.5b00342. Epub 2016 Feb 17. [PubMed:26822114]
  11. Sourbron J, Smolders I, de Witte P, Lagae L: Pharmacological Analysis of the Anti-epileptic Mechanisms of Fenfluramine in scn1a Mutant Zebrafish. Front Pharmacol. 2017 Apr 6;8:191. doi: 10.3389/fphar.2017.00191. eCollection 2017. [PubMed:28428755]
  12. FDA Approved Drug Products: Fintepla (fenfluramine) oral solution [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Opioid receptor activity
Specific Function
Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma m...
Gene Name
SIGMAR1
Uniprot ID
Q99720
Uniprot Name
Sigma non-opioid intracellular receptor 1
Molecular Weight
25127.52 Da
References
  1. Martin P, de Witte PAM, Maurice T, Gammaitoni A, Farfel G, Galer B: Fenfluramine acts as a positive modulator of sigma-1 receptors. Epilepsy Behav. 2020 Apr;105:106989. doi: 10.1016/j.yebeh.2020.106989. Epub 2020 Mar 10. [PubMed:32169824]
  2. Rodriguez-Munoz M, Sanchez-Blazquez P, Garzon J: Fenfluramine diminishes NMDA receptor-mediated seizures via its mixed activity at serotonin 5HT2A and type 1 sigma receptors. Oncotarget. 2018 May 4;9(34):23373-23389. doi: 10.18632/oncotarget.25169. eCollection 2018 May 4. [PubMed:29805740]
  3. Schoonjans AS, Ceulemans B: An Old Drug for a New Indication: Repurposing Fenfluramine From an Anorexigen to an Antiepileptic Drug. Clin Pharmacol Ther. 2019 Nov;106(5):929-932. doi: 10.1002/cpt.1469. Epub 2019 May 22. [PubMed:31116409]
  4. Sourbron J, Smolders I, de Witte P, Lagae L: Pharmacological Analysis of the Anti-epileptic Mechanisms of Fenfluramine in scn1a Mutant Zebrafish. Front Pharmacol. 2017 Apr 6;8:191. doi: 10.3389/fphar.2017.00191. eCollection 2017. [PubMed:28428755]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
Curator comments
It is unclear whether or not 5-HT2A receptor agonism plays a role in reduction of epileptiform activity in Dravet syndrome.
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. Fitzgerald LW, Burn TC, Brown BS, Patterson JP, Corjay MH, Valentine PA, Sun JH, Link JR, Abbaszade I, Hollis JM, Largent BL, Hartig PR, Hollis GF, Meunier PC, Robichaud AJ, Robertson DW: Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine. Mol Pharmacol. 2000 Jan;57(1):75-81. [PubMed:10617681]
  2. Martin P, de Witte PAM, Maurice T, Gammaitoni A, Farfel G, Galer B: Fenfluramine acts as a positive modulator of sigma-1 receptors. Epilepsy Behav. 2020 Apr;105:106989. doi: 10.1016/j.yebeh.2020.106989. Epub 2020 Mar 10. [PubMed:32169824]
  3. Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ: Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells. Br J Pharmacol. 1999 Sep;128(1):13-20. [PubMed:10498829]
  4. Rodriguez-Munoz M, Sanchez-Blazquez P, Garzon J: Fenfluramine diminishes NMDA receptor-mediated seizures via its mixed activity at serotonin 5HT2A and type 1 sigma receptors. Oncotarget. 2018 May 4;9(34):23373-23389. doi: 10.18632/oncotarget.25169. eCollection 2018 May 4. [PubMed:29805740]
  5. Schoonjans AS, Ceulemans B: An Old Drug for a New Indication: Repurposing Fenfluramine From an Anorexigen to an Antiepileptic Drug. Clin Pharmacol Ther. 2019 Nov;106(5):929-932. doi: 10.1002/cpt.1469. Epub 2019 May 22. [PubMed:31116409]
  6. Sourbron J, Schneider H, Kecskes A, Liu Y, Buening EM, Lagae L, Smolders I, de Witte P: Serotonergic Modulation as Effective Treatment for Dravet Syndrome in a Zebrafish Mutant Model. ACS Chem Neurosci. 2016 May 18;7(5):588-98. doi: 10.1021/acschemneuro.5b00342. Epub 2016 Feb 17. [PubMed:26822114]
  7. Sourbron J, Smolders I, de Witte P, Lagae L: Pharmacological Analysis of the Anti-epileptic Mechanisms of Fenfluramine in scn1a Mutant Zebrafish. Front Pharmacol. 2017 Apr 6;8:191. doi: 10.3389/fphar.2017.00191. eCollection 2017. [PubMed:28428755]
  8. FDA Approved Drug Products: Fintepla (fenfluramine) oral solution [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Agonist
Curator comments
Although fenfluramine does exhibit agonist activity at the 5-HT2B receptor, it has been demonstrated that this modulation has no activity in regards to improving seizure control in animal models of Dravet syndrome.
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation...
Gene Name
HTR2B
Uniprot ID
P41595
Uniprot Name
5-hydroxytryptamine receptor 2B
Molecular Weight
54297.41 Da
References
  1. Fitzgerald LW, Burn TC, Brown BS, Patterson JP, Corjay MH, Valentine PA, Sun JH, Link JR, Abbaszade I, Hollis JM, Largent BL, Hartig PR, Hollis GF, Meunier PC, Robichaud AJ, Robertson DW: Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine. Mol Pharmacol. 2000 Jan;57(1):75-81. [PubMed:10617681]
  2. Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL: Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation. 2000 Dec 5;102(23):2836-41. [PubMed:11104741]
  3. Setola V, Hufeisen SJ, Grande-Allen KJ, Vesely I, Glennon RA, Blough B, Rothman RB, Roth BL: 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro. Mol Pharmacol. 2003 Jun;63(6):1223-9. [PubMed:12761331]
  4. Blanpain C, Le Poul E, Parma J, Knoop C, Detheux M, Parmentier M, Vassart G, Abramowicz MJ: Serotonin 5-HT(2B) receptor loss of function mutation in a patient with fenfluramine-associated primary pulmonary hypertension. Cardiovasc Res. 2003 Dec 1;60(3):518-28. [PubMed:14659797]
  5. Kaumann AJ, Levy FO: 5-hydroxytryptamine receptors in the human cardiovascular system. Pharmacol Ther. 2006 Sep;111(3):674-706. [PubMed:16960982]
  6. Roth BL: Drugs and valvular heart disease. N Engl J Med. 2007 Jan 4;356(1):6-9. [PubMed:17202450]
  7. Griffin A, Hamling KR, Knupp K, Hong S, Lee LP, Baraban SC: Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome. Brain. 2017 Mar 1;140(3):669-683. doi: 10.1093/brain/aww342. [PubMed:28073790]
  8. Martin P, de Witte PAM, Maurice T, Gammaitoni A, Farfel G, Galer B: Fenfluramine acts as a positive modulator of sigma-1 receptors. Epilepsy Behav. 2020 Apr;105:106989. doi: 10.1016/j.yebeh.2020.106989. Epub 2020 Mar 10. [PubMed:32169824]
  9. Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ: Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells. Br J Pharmacol. 1999 Sep;128(1):13-20. [PubMed:10498829]
  10. Sourbron J, Schneider H, Kecskes A, Liu Y, Buening EM, Lagae L, Smolders I, de Witte P: Serotonergic Modulation as Effective Treatment for Dravet Syndrome in a Zebrafish Mutant Model. ACS Chem Neurosci. 2016 May 18;7(5):588-98. doi: 10.1021/acschemneuro.5b00342. Epub 2016 Feb 17. [PubMed:26822114]
  11. Sourbron J, Smolders I, de Witte P, Lagae L: Pharmacological Analysis of the Anti-epileptic Mechanisms of Fenfluramine in scn1a Mutant Zebrafish. Front Pharmacol. 2017 Apr 6;8:191. doi: 10.3389/fphar.2017.00191. eCollection 2017. [PubMed:28428755]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Agonist
Curator comments
It is unlikely that fenfluramine exerts any significant effect through the 5-HT1A receptor.
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. Griffin A, Hamling KR, Knupp K, Hong S, Lee LP, Baraban SC: Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome. Brain. 2017 Mar 1;140(3):669-683. doi: 10.1093/brain/aww342. [PubMed:28073790]
  2. Martin P, de Witte PAM, Maurice T, Gammaitoni A, Farfel G, Galer B: Fenfluramine acts as a positive modulator of sigma-1 receptors. Epilepsy Behav. 2020 Apr;105:106989. doi: 10.1016/j.yebeh.2020.106989. Epub 2020 Mar 10. [PubMed:32169824]
  3. Rodriguez-Munoz M, Sanchez-Blazquez P, Garzon J: Fenfluramine diminishes NMDA receptor-mediated seizures via its mixed activity at serotonin 5HT2A and type 1 sigma receptors. Oncotarget. 2018 May 4;9(34):23373-23389. doi: 10.18632/oncotarget.25169. eCollection 2018 May 4. [PubMed:29805740]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
The extent to which fenfluramine inhibits CYP2D6 is unclear; it is unlikely to be relevant at clinically useful concentrations.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Haritos VS, Ching MS, Ghabrial H, Gross AS, Taavitsainen P, Pelkonen O, Battaglia SE, Smallwood RA, Ahokas JT: Metabolism of dexfenfluramine in human liver microsomes and by recombinant enzymes: role of CYP2D6 and 1A2. Pharmacogenetics. 1998 Oct;8(5):423-32. [PubMed:9825834]
  2. von Moltke LL, Greenblatt DJ, Ciraulo DA, Grassi JM, Granda BW, Duan SX, Harmatz JS, Shader RI: Appetite suppressant drugs as inhibitors of human cytochromes P450: in vitro inhibition of P450-2D6 by D- and L-fenfluramine, but not phentermine. J Clin Psychopharmacol. 1998 Aug;18(4):338-41. [PubMed:9690701]
  3. Flockhart Table of Drug Interactions [Link]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  5. FDA Approved Drug Products: Fintepla (fenfluramine) oral solution [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Flockhart Table of Drug Interactions [Link]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  3. FDA Approved Drug Products: Fintepla (fenfluramine) oral solution [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Flockhart Table of Drug Interactions [Link]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  3. FDA Approved Drug Products: Fintepla (fenfluramine) oral solution [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Flockhart Table of Drug Interactions [Link]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  3. FDA Approved Drug Products: Fintepla (fenfluramine) oral solution [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Flockhart Table of Drug Interactions [Link]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  3. FDA Approved Drug Products: Fintepla (fenfluramine) oral solution [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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
  1. Flockhart Table of Drug Interactions [Link]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  3. FDA Approved Drug Products: Fintepla (fenfluramine) oral solution [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
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 oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Flockhart Table of Drug Interactions [Link]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  3. FDA Approved Drug Products: Fintepla (fenfluramine) oral solution [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Substrate
Inhibitor
Curator comments
Fenfluramine, as well as its active metabolite norfenfluramine, are substrates for the SERT transporter. Through an incompletely understood mechanism, potentially involving ion exchange, the transport of these compounds results in a reversal of SERT transport and an increase in extracellular 5-HT.
General Function
Serotonin:sodium symporter activity
Specific Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. Rothman RB, Zolkowska D, Baumann MH: Serotonin (5-HT) transporter ligands affect plasma 5-HT in rats. Ann N Y Acad Sci. 2008 Oct;1139:268-84. doi: 10.1196/annals.1432.042. [PubMed:18991872]
  2. Xie T, Tong L, McLane MW, Hatzidimitriou G, Yuan J, McCann U, Ricaurte G: Loss of serotonin transporter protein after MDMA and other ring-substituted amphetamines. Neuropsychopharmacology. 2006 Dec;31(12):2639-51. Epub 2006 Jan 25. [PubMed:16452989]
  3. Johnson GJ, Leis LA, Dunlop PC, Weir EK: The effect of the anorectic agent, d-fenfluramine, and its primary metabolite, d-norfenfluramine, on intact human platelet serotonin uptake and efflux. J Thromb Haemost. 2003 Dec;1(12):2663-8. [PubMed:14675103]
  4. Rothman RB, Baumann MH, Blough BE, Jacobson AE, Rice KC, Partilla JS: Evidence for noncompetitive modulation of substrate-induced serotonin release. Synapse. 2010 Nov;64(11):862-9. doi: 10.1002/syn.20804. [PubMed:20842720]
  5. Baumann MH, Bulling S, Benaderet TS, Saha K, Ayestas MA, Partilla JS, Ali SF, Stockner T, Rothman RB, Sandtner W, Sitte HH: Evidence for a role of transporter-mediated currents in the depletion of brain serotonin induced by serotonin transporter substrates. Neuropsychopharmacology. 2014 May;39(6):1355-65. doi: 10.1038/npp.2013.331. Epub 2013 Nov 28. [PubMed:24287719]
  6. FDA Approved Drug Products: Fintepla (fenfluramine) oral solution [Link]

Drug created on June 13, 2005 07:24 / Updated on July 03, 2020 11:52

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates