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Identification
NameDexfenfluramine
Accession NumberDB01191  (APRD00648)
TypeSmall Molecule
GroupsApproved, Illicit, Withdrawn
Description

Dexfenfluramine, 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 However, following multiple concerns about the cardiovascular side-effects of the drug, such approval was withdrawn.

Structure
Thumb
Synonyms
SynonymLanguageCode
(+)-fenfluramineNot AvailableNot Available
(S)-fenfluramineNot AvailableNot Available
(S)-N-Ethyl-1-[3-(trifluoromethyl)phenyl]propan-2-amineNot AvailableNot Available
D-N-Ethyl-alpha-methyl-m-trifluoromethylphenethylamineNot AvailableNot Available
DexfenfluraminaNot AvailableNot Available
DexfenfluramineNot AvailableNot Available
DexfenfluraminumNot AvailableNot Available
DextrofenfluramineNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AdifaxNot Available
ReduxNot Available
Brand mixturesNot Available
Categories
CAS number3239-44-9
WeightAverage: 231.2573
Monoisotopic: 231.123484132
Chemical FormulaC12H16F3N
InChI KeyDBGIVFWFUFKIQN-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenethylamines
Direct parentAmphetamines and Derivatives
Alternative parentsPolyamines; Dialkylamines; Organofluorides; Alkyl Fluorides
Substituentspolyamine; secondary aliphatic amine; secondary amine; organonitrogen compound; amine; organofluoride; organohalogen; alkyl halide; alkyl fluoride
Classification descriptionThis compound belongs to the amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.
Pharmacology
IndicationFor the management of obesity including weight loss and maintenance of weight loss in patients on a reduced calorie diet
PharmacodynamicsUsed 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 actionDexfenfluramine 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.
AbsorptionWell-absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein binding36%
Metabolism
Route of eliminationNot Available
Half life17-20 hours
ClearanceNot Available
ToxicitySymptoms of overdose include respiratory failure and cardiac arrest leading to death.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9868
Caco-2 permeable + 0.7004
P-glycoprotein substrate Non-substrate 0.5138
P-glycoprotein inhibitor I Non-inhibitor 0.5934
P-glycoprotein inhibitor II Non-inhibitor 0.8383
Renal organic cation transporter Non-inhibitor 0.7404
CYP450 2C9 substrate Non-substrate 0.8506
CYP450 2D6 substrate Substrate 0.8919
CYP450 3A4 substrate Non-substrate 0.6781
CYP450 1A2 substrate Inhibitor 0.8859
CYP450 2C9 substrate Non-inhibitor 0.8616
CYP450 2D6 substrate Inhibitor 0.7253
CYP450 2C19 substrate Non-inhibitor 0.5205
CYP450 3A4 substrate Non-inhibitor 0.5219
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6657
Ames test Non AMES toxic 0.8808
Carcinogenicity Non-carcinogens 0.6397
Biodegradation Not ready biodegradable 0.984
Rat acute toxicity 3.1255 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9666
hERG inhibition (predictor II) Inhibitor 0.7811
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
CapsuleOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP3.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0215ALOGPS
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
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD07805
ChEBI439329
ChEMBLCHEMBL248702
Therapeutic Targets DatabaseDAP001224
PharmGKBPA164747936
RxListhttp://www.rxlist.com/cgi/generic/dexfen.htm
WikipediaDexfenfluramine
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(49.1 KB)
Interactions
Drug Interactions
Drug
AcetophenazineDecreased anorexic effect, may increase psychotic symptoms
AlimemazineDecreased anorexic effect, may increase psychotic symptoms
ChlorpromazineDecreased anorexic effect, may increase psychotic symptoms.
EthopropazineDecreased anorexic effect, may increase psychotic symptoms
FluoxetineRisk of serotoninergic syndrome
FluphenazineDecreased anorexic effect, may increase psychotic symptoms
FluvoxamineRisk of serotoninergic syndrome
GuanethidineDexfenfluramine may decrease the effect of guanethidine.
Insulin AspartFenfluramine increases the effect of insulin
Insulin DetemirFenfluramine increases the effect of insulin
Insulin GlulisineFenfluramine increases the effect of insulin
IsocarboxazidRisk of hypertensive crisis.
MesoridazineDecreased anorexic effect, may increase psychotic symptoms
MethdilazineDecreased anorexic effect, may increase psychotic symptoms
MethotrimeprazineDecreased anorexic effect, may increase psychotic symptoms
ParoxetineRisk of serotoninergic syndrome
PerphenazineDecreased anorexic effect, may increase psychotic symptoms
PhenelzinePossible hypertensive crisis
ProchlorperazineDecreased anorexic effect, may increase psychotic symptoms.
PromazineDecreased anorexic effect, may increase psychotic symptoms
PromethazineDecreased anorexic effect, may increase pyschotic symptoms.
PropericiazineDecreased anorexic effect, may increase psychotic symptoms.
PropiomazineDecreased anorexic effect, may increase psychotic symptoms
RasagilinePossible hypertensive crisis
ThiethylperazineDecreased anorexic effect, may increase psychotic symptoms
ThioridazineDecreased anorexic effect, may increase psychotic symptoms
TranylcyprominePossible hypertensive crisis
TrifluoperazineDecreased anorexic effect, may increase psychotic symptoms
TriflupromazineDecreased anorexic effect, may increase psychotic symptoms
VenlafaxineRisk of serotoninergic syndrome
Food Interactions
  • Take with meals.

Targets

1. Sodium-dependent serotonin transporter

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent serotonin transporter P31645 Details

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. Pubmed
  2. Russell BR, Laverty R: The effect of®-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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed

2. 5-hydroxytryptamine receptor 2C

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2C P28335 Details

References:

  1. Vickers SP, Clifton PG, Dourish CT, Tecott LH: Reduced satiating effect of d-fenfluramine in serotonin 5-HT receptor mutant mice. Psychopharmacology (Berl). 1999 Apr;143(3):309-14. Pubmed
  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. Pubmed
  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. Pubmed
  4. Tomkins DM, Joharchi N, Tampakeras M, Martin JR, Wichmann J, Higgins GA: An investigation of the role of 5-HT receptors in modifying ethanol self-administration behaviour. Pharmacol Biochem Behav. 2002 Apr;71(4):735-44. Pubmed
  5. Bickerdike MJ: 5-HT2C receptor agonists as potential drugs for the treatment of obesity. Curr Top Med Chem. 2003;3(8):885-97. Pubmed

Enzymes

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2A6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2A6 P11509 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13