NAV

Dexfenfluramine

Identification

Generic Name
Dexfenfluramine
DrugBank Accession Number
DB01191
Background

Dexfenfluramine, also marketed under the name Redux, is a serotoninergic anorectic drug. For a fairly limited time during the middle of the nineties, the US FDA had approved it for use in managing weight loss. However, following multiple concerns about the cardiovascular side-effects of the drug, such approval was withdrawn.

Type
Small Molecule
Groups
Approved, Illicit, Investigational, Withdrawn
Structure
3D
Similar Structures
Weight
Average: 231.2573
Monoisotopic: 231.123484132
Chemical Formula
C12H16F3N
Synonyms
  • (+)-fenfluramine
  • (S)-fenfluramine
  • (S)-N-ethyl-1-[3-(trifluoromethyl)phenyl]propan-2-amine
  • d-N-ethyl-α-methyl-m-trifluoromethylphenethylamine
  • Dexfenfluramina
  • Dexfenfluramine
  • Dexfenfluraminum
  • Dextrofenfluramine
External IDs
  • J13.711A
  • S 5614
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Pharmacology

Indication

For the management of obesity including weight loss and maintenance of weight loss in patients on a reduced calorie diet

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Used to treat diabetes and obesity, Dexfenfluramine decreases caloric intake by increasing serotonin levels in the brain’s synapses. Dexfenfluramine acts as a serotonin reuptake inhibitor. It also causes release of serotonin from the synaptosomes.

Mechanism of action

Dexfenfluramine binds to the serotonin reuptake pump. This causes inhbition of serotonin reuptake. The increased levels of serotonin lead to greater serotonin receptor activation which in turn lead to enhancement of serotoninergic transmission in the centres of feeding behavior located in the hypothalamus. This suppresses the appetite for carbohydrates.

TargetActionsOrganism
ASodium-dependent serotonin transporter
inhibitor
Humans
U5-hydroxytryptamine receptor 2C
agonist
Humans
Absorption

Well-absorbed from the gastrointestinal tract.

Volume of distribution

Not Available

Protein binding

36%

Metabolism
Not Available
Route of elimination

Not Available

Half-life

17-20 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Symptoms of overdose include respiratory failure and cardiac arrest leading to death.

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);">
Not Available

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.
DrugInteraction
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interactions in your software
AbametapirThe serum concentration of Dexfenfluramine can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Dexfenfluramine can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Dexfenfluramine can be increased when it is combined with Abiraterone.
AcebutololThe metabolism of Dexfenfluramine can be decreased when combined with Acebutolol.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Dexfenfluramine.
Food Interactions
  • Take with food.

Products

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International/Other Brands
Adifax / Redux

Categories

ATC Codes
A08AA04 — Dexfenfluramine
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
fenfluramine (CHEBI:439329)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
E35R3G56OV
CAS number
3239-44-9
InChI Key
DBGIVFWFUFKIQN-VIFPVBQESA-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/t9-/m0/s1
IUPAC Name
ethyl[(2S)-1-[3-(trifluoromethyl)phenyl]propan-2-yl]amine
SMILES
CCN[C@@H](C)CC1=CC=CC(=C1)C(F)(F)F

References

General References
Not Available
Human Metabolome Database
HMDB0015322
KEGG Drug
D07805
PubChem Compound
66265
PubChem Substance
46508388
ChemSpider
59646
BindingDB
85596
RxNav
3268
ChEBI
439329
ChEMBL
CHEMBL248702
ZINC
ZINC000000000294
Therapeutic Targets Database
DAP001224
PharmGKB
PA164747936
RxList
RxList Drug Page
Wikipedia
Dexfenfluramine
MSDS
Download (49.1 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
Not AvailableCompletedBasic ScienceAmphetamine Abuse / Amphetamine-Related Disorders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP3.5Not Available
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 GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-00di-9110000000-1bb444f1022b28d94dc0
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-001r-0590000000-41fdbf4e990aeb07fedd
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001l-4390000000-8ba6d74f7a2fbe2b3443
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0aos-5930000000-0d3665493f9a45d1d08d
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0920000000-2cf79ebe58e294369ed6
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4l-2900000000-eeed4b532d6aeaa332db
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-01b9-1910000000-f786fd358d0f0f5e67bc
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-153.0467367
predicted
DarkChem Lite v0.1.0
[M-H]-154.55128
predicted
DeepCCS 1.0 (2019)
[M+H]+154.0410367
predicted
DarkChem Lite v0.1.0
[M+H]+156.90929
predicted
DeepCCS 1.0 (2019)
[M+Na]+153.6159367
predicted
DarkChem Lite v0.1.0
[M+Na]+163.00551
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Details1. Sodium-dependent serotonin transporter
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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. Eddahibi S, Adnot S, Frisdal E, Levame M, Hamon M, Raffestin B: Dexfenfluramine-associated changes in 5-hydroxytryptamine transporter expression and development of hypoxic pulmonary hypertension in rats. J Pharmacol Exp Ther. 2001 Apr;297(1):148-54. [Article]
  2. Russell BR, Laverty R: The effect of (R)-HA966 or ACEA 1021 on dexfenfluramine or (S)-MDMA-induced changes in temperature, activity, and neurotoxicity. Pharmacol Biochem Behav. 2001 Mar;68(3):565-74. [Article]
  3. 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. [Article]
  4. 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. [Article]
  5. Wang X, Baumann MH, Xu H, Rothman RB: 3,4-methylenedioxymethamphetamine (MDMA) administration to rats decreases brain tissue serotonin but not serotonin transporter protein and glial fibrillary acidic protein. Synapse. 2004 Sep 15;53(4):240-8. [Article]
Details2. 5-hydroxytryptamine receptor 2C
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Vickers SP, Clifton PG, Dourish CT, Tecott LH: Reduced satiating effect of d-fenfluramine in serotonin 5-HT(2C) receptor mutant mice. Psychopharmacology (Berl). 1999 Apr;143(3):309-14. [Article]
  2. Wilson AW, Costall B, Neill JC: Manipulation of operant responding for an ethanol-paired conditioned stimulus in the rat by pharmacological alteration of the serotonergic system. J Psychopharmacol. 2000;14(4):340-6. [Article]
  3. Vickers SP, Dourish CT, Kennett GA: Evidence that hypophagia induced by d-fenfluramine and d-norfenfluramine in the rat is mediated by 5-HT2C receptors. Neuropharmacology. 2001 Aug;41(2):200-9. [Article]
  4. Tomkins DM, Joharchi N, Tampakeras M, Martin JR, Wichmann J, Higgins GA: An investigation of the role of 5-HT(2C) receptors in modifying ethanol self-administration behaviour. Pharmacol Biochem Behav. 2002 Apr;71(4):735-44. [Article]
  5. Bickerdike MJ: 5-HT2C receptor agonists as potential drugs for the treatment of obesity. Curr Top Med Chem. 2003;3(8):885-97. [Article]

Enzymes

Details1. Cytochrome P450 1A2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Data supporting this action is limited to in vitro studies.
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. 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. [Article]
Details2. Cytochrome P450 2E1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. 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. [Article]
Details3. Cytochrome P450 2D6
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. [Article]
  2. Gross AS, Phillips AC, Rieutord A, Shenfield GM: The influence of the sparteine/debrisoquine genetic polymorphism on the disposition of dexfenfluramine. Br J Clin Pharmacol. 1996 Apr;41(4):311-7. [Article]
  3. Flockhart Table of Drug Interactions [Link]

Drug created at June 13, 2005 13:24 / Updated at May 07, 2021 21:26