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Identification
Name Dexfenfluramine
Accession Number DB01191 (APRD00648)
Type small molecule
Groups illicit, approved, withdrawn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 However, following multiple concerns about the cardiovascular side-effects of the drug, such approval was withdrawn.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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
(+)-fenfluramine
(S)-fenfluramine
Dextrofenfluramine
Salts Not Available
Brand names
Name Company
Adifax
Redux
Brand mixtures Not Available
Categories
  • Appetite Depressants
  • Serotonin Agonists
  • Serotonin reuptake inhibitor
  • Antiobesity Agents
CAS number 3239-44-9
Weight Average: 231.2573
Monoisotopic: 231.123484132
Chemical Formula C12H16F3N
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For the management of obesity including weight loss and maintenance of weight loss in patients on a reduced calorie diet
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.
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
Toxicity Symptoms of overdose include respiratory failure and cardiac arrest leading to death.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms
Form Route Strength
Capsule Oral
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
logP 3.5 Not Available
Predicted Properties
Property Value Source
water solubility 2.15e-02 g/l ALOGPS
logP 3.3 ALOGPS
logP 3.47 ChemAxon
logS -4 ALOGPS
pKa (strongest basic) 10.22 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 1 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 12.03 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 59.2 ChemAxon
polarizability 22.69 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D07805 Link_out
ChEBI 439329 Link_out
ChEMBL 439329 Link_out
Therapeutic Targets Database DAP001224 Link_out
PharmGKB PA164747936 Link_out
RxList http://www.rxlist.com/cgi/generic/dexfen.htm Link_out
Wikipedia http://en.wikipedia.org/wiki/Dexfenfluramine Link_out
ATC Codes
  • A08AA04
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (49.1 KB)
Interactions
Drug Interactions
Drug Interaction
Acetophenazine Decreased anorexic effect, may increase psychotic symptoms
Chlorpromazine Decreased anorexic effect, may increase psychotic symptoms.
Ethopropazine Decreased anorexic effect, may increase psychotic symptoms
Fluoxetine Risk of serotoninergic syndrome
Fluphenazine Decreased anorexic effect, may increase psychotic symptoms
Fluvoxamine Risk of serotoninergic syndrome
Guanethidine Dexfenfluramine may decrease the effect of guanethidine.
Insulin Fenfluramine increases the effect of insulin
Insulin Aspart Fenfluramine increases the effect of insulin
Insulin Detemir Fenfluramine increases the effect of insulin
Insulin Glulisine Fenfluramine increases the effect of insulin
Isocarboxazid Risk of hypertensive crisis.
Mesoridazine Decreased anorexic effect, may increase psychotic symptoms
Methdilazine Decreased anorexic effect, may increase psychotic symptoms
Methotrimeprazine Decreased anorexic effect, may increase psychotic symptoms
Paroxetine Risk of serotoninergic syndrome
Perphenazine Decreased anorexic effect, may increase psychotic symptoms
Phenelzine Possible hypertensive crisis
Prochlorperazine Decreased anorexic effect, may increase psychotic symptoms.
Promazine Decreased anorexic effect, may increase psychotic symptoms
Promethazine Decreased anorexic effect, may increase pyschotic symptoms.
Propericiazine Decreased anorexic effect, may increase psychotic symptoms.
Propiomazine Decreased anorexic effect, may increase psychotic symptoms
Rasagiline Possible hypertensive crisis
Thiethylperazine Decreased anorexic effect, may increase psychotic symptoms
Thioridazine Decreased anorexic effect, may increase psychotic symptoms
Tranylcypromine Possible hypertensive crisis
Trifluoperazine Decreased anorexic effect, may increase psychotic symptoms
Triflupromazine Decreased anorexic effect, may increase psychotic symptoms
Trimeprazine Decreased anorexic effect, may increase psychotic symptoms
Venlafaxine Risk of serotoninergic syndrome
Food Interactions
  • Take with meals.
Targets

1. Sodium-dependent serotonin transporter

Pharmacological action: yes
Actions: inhibitor

Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P31645 Link_out
Gene: SLC6A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 2C receptor

Pharmacological action: unknown
Actions: agonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P28335 Link_out
Gene: HTR2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor

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 antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase

UniProt ID: P11509 Link_out
Gene: CYP2A6
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

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 imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

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 or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19