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Record Information
Version2.0
Creation Date2009-07-21 20:28:35 UTC
Update Date2014-12-24 20:25:55 UTC
Accession NumberT3D3014
Identification
Common NameDexfenfluramine
ClassSmall Molecule
DescriptionDexfenfluramine, also marketed under the name Redux, is a serotoninergic anorectic drug. It was for some years in the mid-1990s approved by the United States Food and Drug Administration for the purposes of weight loss. However, following multiple concerns about the cardiovascular side-effects of the drug, such approval was withdrawn.
Compound Type
  • Amine
  • Anti-Obesity Agent
  • Appetite Depressant
  • Drug
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Organofluoride
  • Serotonin Agonist
  • Serotonin Receptor Agonist
  • Serotonin Reuptake Inhibitor
  • Serotonin Uptake Inhibitor
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+)-fenfluramine
(S)-fenfluramine
(S)-N-Ethyl-1-[3-(trifluoromethyl)phenyl]propan-2-amine
Adifax
D-N-Ethyl-alpha-methyl-m-trifluoromethylphenethylamine
Dexfenfluramina
Dexfenfluraminum
Dextrofenfluramine
Redux
Chemical FormulaC12H16F3N
Average Molecular Mass231.257 g/mol
Monoisotopic Mass231.123 g/mol
CAS Registry Number3239-44-9
IUPAC Nameethyl[(2S)-1-[3-(trifluoromethyl)phenyl]propan-2-yl]amine
Traditional Namedexfenfluramine
SMILES[H][C@](C)(CC1=CC(=CC=C1)C(F)(F)F)NCC
InChI IdentifierInChI=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
InChI KeyInChIKey=DBGIVFWFUFKIQN-VIFPVBQESA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenethylamines
Direct ParentAmphetamines and derivatives
Alternative Parents
Substituents
  • Amphetamine or derivatives
  • Trifluoromethylbenzene
  • Phenylpropane
  • Aralkylamine
  • Secondary aliphatic amine
  • Secondary amine
  • Alkyl fluoride
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Organopnictogen compound
  • Organic nitrogen compound
  • Amine
  • Alkyl halide
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility2.15e-02 g/L
LogP3.5
Predicted Properties
PropertyValueSource
Water Solubility0.022 g/LALOGPS
logP3.3ALOGPS
logP3.47ChemAxon
logS-4ALOGPS
pKa (Strongest Basic)10.22ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area12.03 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity59.2 m³·mol⁻¹ChemAxon
Polarizability22.69 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00di-9110000000-1bb444f1022b28d94dc0JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-1190000000-7fbe4443e51aea6826c3JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001r-8890000000-5cd73b17e1103d99e7fbJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00ov-9610000000-58d820854fe8992bc6a3JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0090000000-96055c6c721aecfc76f8JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-2190000000-2f8c88fb4bc53943412fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9410000000-a342d0ae14c5230c00a4JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0290000000-ac3db862ce9c06ed67f5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-0910000000-6cb4ba049f7be32b0f1cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-1900000000-43131e1ffc852067efa9JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0090000000-8ae4a9b01f14913328e8JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a5i-0930000000-c301feb5a0d5278285b2JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-0900000000-30767724225603e597e1JSpectraViewer
Toxicity Profile
Route of ExposureWell-absorbed from the gastrointestinal tract.
Mechanism of ToxicityDexfenfluramine 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.
Metabolism Half Life: 17-20 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesA serotoninergic anorectic drug once used for the purposes of weight loss, but pulled out from the global market following multiple concerns about the cardiovascular side-effects of the drug. [Wikipedia]
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include respiratory failure and cardiac arrest leading to death.
TreatmentGeneral supportive measures for oral drug overdose should be instituted. Measures that have been used in dexfenfluramine overdose cases include aspiration of gastric contents, gastric lavage with activated charcoal, osmotic diuresis, forced acid diuresis, and careful monitoring of CNS or respiratory depression. The effectiveness of dialysis is not known. Patients should be followed closely until there is no further evidence of drug-related CNS effects. No specific therapy for dexfenfluramine overdose is known. (3)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01191
HMDB IDHMDB15322
PubChem Compound ID66265
ChEMBL IDCHEMBL248702
ChemSpider ID59646
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID439329
BioCyc IDNot Available
CTD IDNot Available
Stitch IDDexfenfluramine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkDexfenfluramine
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Kalia M: Reversible, short-lasting, and dose-dependent effect of (+)-fenfluramine on neocortical serotonergic axons. Brain Res. 1991 May 10;548(1-2):111-25. [1868326 ]
  3. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.
Gene Name:
HTR2C
Uniprot ID:
P28335
Molecular Weight:
51820.705 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory2.08 uMNot AvailableBindingDB 85596
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. 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. [10617681 ]
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 substances, such as lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.
Gene Name:
HTR1B
Uniprot ID:
P28222
Molecular Weight:
43567.535 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
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 change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain. Plays a role in the regulation of behavior, including impulsive behavior. Required for normal proliferation of embryonic cardiac myocytes and normal heart development. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. Required for normal proliferation of the interstitial cells of Cajal in the intestine.
Gene Name:
HTR2B
Uniprot ID:
P41595
Molecular Weight:
54297.41 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory3.92 uMNot AvailableBindingDB 85596
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. [10617681 ]
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 the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:
SLC6A4
Uniprot ID:
P31645
Molecular Weight:
70324.165 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]