Dexfenfluramine
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Basic Info
| Common Name | Dexfenfluramine(F04787) |
| 2D Structure | |
| 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 However, following multiple concerns about the cardiovascular side-effects of the drug, such approval was withdrawn. |
| FRCD ID | F04787 |
| CAS Number | 3239-44-9 |
| PubChem CID | 66265 |
| Formula | C12H16F3N |
| IUPAC Name | (2S)-N-ethyl-1-[3-(trifluoromethyl)phenyl]propan-2-amine |
| 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 |
| Canonical SMILES | CCNC(C)CC1=CC(=CC=C1)C(F)(F)F |
| Isomeric SMILES | CCN[C@@H](C)CC1=CC(=CC=C1)C(F)(F)F |
| Wikipedia | Dexfenfluramine |
| Synonyms |
(+)-Fenfluramine
Dexfenfluramine
Dextrofenfluramine
(S)-Fenfluramine
d-Fenfluramine
Dexfenfluramina
Dexfenfluraminum
Adifax
3239-44-9
Redux
|
| Classifies |
Illegal Additives
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Benzenoids |
| Class | Benzene and substituted derivatives |
| Subclass | Phenethylamines |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Amphetamines and derivatives |
| Alternative Parents | |
| Molecular Framework | Aromatic homomonocyclic compounds |
| 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 |
| 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. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 231.262 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 4 |
| Complexity | 203 |
| Monoisotopic Mass | 231.123 |
| Exact Mass | 231.123 |
| XLogP | 3.4 |
| Formal Charge | 0 |
| Heavy Atom Count | 16 |
| Defined Atom Stereocenter Count | 1 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9868 |
| Human Intestinal Absorption | HIA+ | 1.0000 |
| Caco-2 Permeability | Caco2+ | 0.7004 |
| P-glycoprotein Substrate | Non-substrate | 0.5138 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.5934 |
| Non-inhibitor | 0.8383 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.7404 |
| Distribution | ||
| Subcellular localization | Lysosome | 0.8604 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8506 |
| CYP450 2D6 Substrate | Substrate | 0.8919 |
| CYP450 3A4 Substrate | Non-substrate | 0.6781 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.8859 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.8616 |
| CYP450 2D6 Inhibitor | Inhibitor | 0.7253 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.5205 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.5219 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.6657 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9666 |
| Inhibitor | 0.7811 | |
| AMES Toxicity | Non AMES toxic | 0.8808 |
| Carcinogens | Non-carcinogens | 0.6397 |
| Fish Toxicity | High FHMT | 0.9688 |
| Tetrahymena Pyriformis Toxicity | High TPT | 1.0000 |
| Honey Bee Toxicity | Low HBT | 0.5474 |
| Biodegradation | Not ready biodegradable | 0.9840 |
| Acute Oral Toxicity | II | 0.7268 |
| Carcinogenicity (Three-class) | Non-required | 0.7418 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.0061 | LogS |
| Caco-2 Permeability | 1.4559 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 3.1255 | LD50, mol/kg |
| Fish Toxicity | 1.1232 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 1.1196 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| [Determination of the optical purity of N-nitrosofenfluramine found in the Chinese slimming diet]. | Yakugaku Zasshi | 2003 Sep | 14513772 |
| Diet drug-related cardiac valve disease: the Mayo Clinic echocardiographic laboratory experience. | Mayo Clin Proc | 2000 May | 10807073 |
| [Appetite suppressants and heart valve disorders]. | Arch Mal Coeur Vaiss | 1999 Sep | 10533670 |
| Brain serotonin neurotoxicity and primary pulmonary hypertension from fenfluramine and dexfenfluramine. A systematic review of the evidence. | JAMA | 1997 Aug 27 | 9272900 |
| Peripherally and centrally administered bombesin induce Fos-like immunoreactivity in different brain regions in rats. | Regul Pept | 1996 Apr 23 | 8795081 |
| Reversal of dexfenfluramine-induced anorexia and c-Fos/c-Jun expression by lesion in the lateral parabrachial nucleus. | Brain Res | 1994 Mar 21 | 8004454 |
| Acute dexfenfluramine administration normalizes glucose tolerance in rats with insulin-deficient diabetes. | Eur J Clin Invest | 1994 Mar | 8033952 |
Targets
- 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
- Mechanism of Action:
- Dexfenfluramine binds to the serotonin reuptake pump. This causes inhbition of serotonin uptake and release of serotonin. 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.
References
- 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
References
- 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
- Mechanism of Action:
- Dexfenfluramine binds to the serotonin reuptake pump. This causes inhbition of serotonin uptake and release of serotonin. 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.
References
- 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 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
- Mechanism of Action:
- Dexfenfluramine binds to the serotonin reuptake pump. This causes inhbition of serotonin uptake and release of serotonin. 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.
References
- 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 ]