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Identification
Name Phentermine
Accession Number DB00191 (APRD00093)
Type small molecule
Groups illicit, approved
Description

A central nervous system stimulant and sympathomimetic with actions and uses similar to those of dextroamphetamine. It has been used most frequently in the treatment of obesity. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • (alpha,alpha)-Dimethylphenethylamine
  • Phentermine Hcl
  • Phentermine Hydrochloride
Brand names
  • Adipex-P
  • Duromine
  • Fastin
  • Inoamin
  • Ionamin
  • Linyl
  • Lipopill
  • Lonamin
  • Mirapront
  • Normephentermine
  • Obenix
  • Obestin-30
  • Oby-Trim
  • Omnibex
  • Ona Mast
  • Ona-Mast
  • Phentercot
  • Phentermine Resin 30
  • Phentride
  • Pre-Sate
  • Pro-Fast
  • Teramine
  • Tora
  • Uritone
  • Wilpo
  • Wyamine Sulfate
  • Zantryl
Brand name mixtures
  • Fen-phen (fenfluramine + phentermine)
Categories
  • Adrenergic Agents
  • Central Nervous System Stimulants
  • Sympathomimetics
  • Central Nervous System Agents
  • Appetite Depressants
  • Anorexigenic Agents
  • Stimulants
CAS number 122-09-8
Weight Average: 149.2328
Monoisotopic: 149.120449485
Chemical Formula C10H15N
InChI Key InChIKey=DHHVAGZRUROJKS-UHFFFAOYSA-N
InChI
InChI=1S/C10H15N/c1-10(2,11)8-9-6-4-3-5-7-9/h3-7H,8,11H2,1-2H3
Plain Text
IUPAC Name
2-methyl-1-phenylpropan-2-amine
SMILES
CC(C)(N)CC1=CC=CC=C1
Plain Text
Mass Spec show (7.3 KB)
Taxonomy
Kingdom Organic
Classes
  • Phenethylamines
  • Amphetamines
Substructures
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Phenethylamines
  • Aromatic compounds
  • Amphetamines
Pharmacology
Indication For the treatment and management of obesity.
Pharmacodynamics Phentermine is indicated in the management of exogenous obesity as a short term (a few weeks) adjunct in a regimen of weight reduction based on caloric restriction. Phentermine hydrochloride is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, the amphetamines. Actions include central nervous system stimulation and elevation of blood pressure. Tachyphylaxis and tolerance have been demonstrated with all drugs of this class in which these phenomena have been looked for.
Mechanism of action Phentermine is an amphetamine that stimulates neurons to release or maintain high levels of a particular group of neurotransmitters known as catecholamines; these include dopamine and norepinephrine. High levels of these catecholamines tend to suppress hunger signals and appetite. The drug seems to inhibit reuptake of noradrenaline, dopamine, and seratonin through inhibition or reversal of the reuptake transporters. It may also inhibit MAO enzymes leaving more neurotransmitter available at the synapse.Phentermine (through catecholamine elevation) may also indirectly affect leptin levels in the brain. It is theorized that phentermine can raise levels of leptin which signal satiety. It is also theorized that increased levels of the catecholamines are partially responsible for halting another chemical messenger known as neuropeptide Y. This peptide initiates eating, decreases energy expenditure, and increases fat storage.
Absorption Phentermine is rapidly absorbed after oral ingestion.
Volume of distribution Not Available
Protein binding Approximately 96.3%
Metabolism

Hepatic.
Route of elimination Not Available
Half life 16 to 31 hours
Clearance Not Available
Toxicity LD50 is adult monkeys is 15 to 20 mg/kg. Symptoms of overdose include delirium, mania, self-injury, marked hypertension, tachycardia, arrhythmia, hyperpyrexia, convulsion, coma, and circulatory collapse.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Baxter healthcare corp anesthesia critical care
  • Teva pharmaceuticals usa inc
  • Glaxosmithkline
  • Ferndale laboratories inc
  • Shire richwood inc
  • Mm mast and co
  • Abc holding corp
  • Able laboratories inc
  • Actavis totowa llc
  • Barr laboratories inc
  • Camall co inc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Ivax pharmaceuticals inc
  • Kvk tech inc
  • Lannett co inc
  • Lannett holdings inc
  • Mutual pharmaceutical co inc
  • Sandoz inc
  • Tg united inc
  • Tg united labs llc
  • Usl pharma inc
  • Vitarine pharmaceuticals inc
  • Watson laboratories inc
  • Actavis elizabeth llc
  • Caraco pharmaceutical laboratories ltd
  • Vintage pharmaceuticals inc
  • Solvay pharmaceuticals
  • Ucb inc
  • Quantum pharmics ltd
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Prices
Unit description Cost Unit
Phentermine hcl powder 10.71 USD g
Ionamin 30 mg capsule sa 2.87 USD capsule
Adipex-P 37.5 mg capsule 2.2 USD capsule
Adipex-p 37.5 mg tablet 2.15 USD tablet
Phentermine 37.5 mg tablet 1.54 USD tablet
Phentermine HCl 15 mg capsule 1.18 USD capsule
Phentermine HCl 30 mg capsule 1.17 USD capsule
Ionamin 15 mg capsule sa 1.15 USD capsule
Phentermine HCl 37.5 mg capsule 1.0 USD capsule
Phentermine HCl 37.5 mg tablet 1.0 USD tablet
Phentermine 8 mg tablet 0.54 USD tablet
Patents Not Available
Properties
State solid
Melting point 205 oC
Experimental Properties
Property Value Source
water solubility 18.6 g/L PhysProp
logP 2.2 PhysProp
Predicted Properties
Property Value Source
water solubility 7.57e-01 g/l ALOGPS
logP 2.32 ALOGPS
logP 2.08 ChemAxon Molconvert
logS -2.29 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 1 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 26.02 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 48.34 ChemAxon Molconvert
polarizability 17.88 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Bray GA: A concise review on the therapeutics of obesity. Nutrition. 2000 Oct;16(10):953-60. Pubmed
  2. Nelson DL, Gehlert DR: Central nervous system biogenic amine targets for control of appetite and energy expenditure. Endocrine. 2006 Feb;29(1):49-60. Pubmed
External Links
Resource Link
KEGG Drug D05458 Link_out
KEGG Compound C07438 Link_out
PubChem Compound 4771 Link_out
PubChem Substance 46508515 Link_out
ChemSpider 4607 Link_out
ChEBI 8080 Link_out
ChEMBL 8080 Link_out
Therapeutic Targets Database DAP000719 Link_out
PharmGKB PA450923 Link_out
Drug Product Database 891770 Link_out
RxList http://www.rxlist.com/cgi/generic/phenterm.htm Link_out
Drugs.com http://www.drugs.com/phentermine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Phentermine Link_out
ATC Codes
  • A08AA01
  • C01CA11
AHFS Codes
  • 28:20.92
PDB Entries Not Available
FDA label show (159 KB)
MSDS show (48.2 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Limit caffeine intake.
  • Take without regard to meals.
Targets

1. Sodium-dependent noradrenaline transporter

Pharmacological action: yes
Actions: inhibitor

Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P23975 Link_out
Gene: SLC6A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Stephens LC, Katz SG: Phentermine and anaesthesia. Anaesth Intensive Care. 2005 Aug;33(4):525-7. Pubmed
  4. Samanin R, Garattini S: Neurochemical mechanism of action of anorectic drugs. Pharmacol Toxicol. 1993 Aug;73(2):63-8. Pubmed
  5. Proietto J, Fam BC, Ainslie DA, Thorburn AW: Novel anti-obesity drugs. Expert Opin Investig Drugs. 2000 Jun;9(6):1317-26. Pubmed

2. 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. John CE, Jones SR: Voltammetric characterization of the effect of monoamine uptake inhibitors and releasers on dopamine and serotonin uptake in mouse caudate-putamen and substantia nigra slices. Neuropharmacology. 2007 Jun;52(8):1596-605. Epub 2007 Mar 16. Pubmed
  2. 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
  3. Mekontso-Dessap A, Brouri F, Pascal O, Lechat P, Hanoun N, Lanfumey L, Seif I, Benhaiem-Sigaux N, Kirsch M, Hamon M, Adnot S, Eddahibi S: Deficiency of the 5-hydroxytryptamine transporter gene leads to cardiac fibrosis and valvulopathy in mice. Circulation. 2006 Jan 3;113(1):81-9. Epub 2005 Dec 27. Pubmed
  4. Rothman RB, Ayestas MA, Dersch CM, Baumann MH: Aminorex, fenfluramine, and chlorphentermine are serotonin transporter substrates. Implications for primary pulmonary hypertension. Circulation. 1999 Aug 24;100(8):869-75. Pubmed
  5. Zolkowska D, Rothman RB, Baumann MH: Amphetamine analogs increase plasma serotonin: implications for cardiac and pulmonary disease. J Pharmacol Exp Ther. 2006 Aug;318(2):604-10. Epub 2006 Apr 27. Pubmed

3. Sodium-dependent dopamine transporter

Pharmacological action: yes
Actions: inhibitor

Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: Q01959 Link_out
Gene: SLC6A3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. John CE, Jones SR: Voltammetric characterization of the effect of monoamine uptake inhibitors and releasers on dopamine and serotonin uptake in mouse caudate-putamen and substantia nigra slices. Neuropharmacology. 2007 Jun;52(8):1596-605. Epub 2007 Mar 16. Pubmed
  2. Gruner JA, Marcy VR, Lin YG, Bozyczko-Coyne D, Marino MJ, Gasior M: The roles of dopamine transport inhibition and dopamine release facilitation in wake enhancement and rebound hypersomnolence induced by dopaminergic agents. Sleep. 2009 Nov 1;32(11):1425-38. Pubmed

4. Amine oxidase [flavin-containing] A

Pharmacological action: yes
Actions: antagonist

Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine

Organism class: human
UniProt ID: P21397 Link_out
Gene: MAOA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Rothman RB: Is phentermine an inhibitor of monoamine oxidase? A critical appraisal. Synapse. 1999 May;32(2):141-5. Pubmed
  2. Ulus IH, Maher TJ, Wurtman RJ: Characterization of phentermine and related compounds as monoamine oxidase (MAO) inhibitors. Biochem Pharmacol. 2000 Jun 15;59(12):1611-21. Pubmed
  3. Kilpatrick IC, Traut M, Heal DJ: Monoamine oxidase inhibition is unlikely to be relevant to the risks associated with phentermine and fenfluramine: a comparison with their abilities to evoke monoamine release. Int J Obes Relat Metab Disord. 2001 Oct;25(10):1454-8. Pubmed
  4. Nandigama RK, Newton-Vinson P, Edmondson DE: Phentermine inhibition of recombinant human liver monoamine oxidases A and B. Biochem Pharmacol. 2002 Mar 1;63(5):865-9. Pubmed

5. Amine oxidase [flavin-containing] B

Pharmacological action: yes
Actions: antagonist

Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine

Organism class: human
UniProt ID: P27338 Link_out
Gene: MAOB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Rothman RB: Does phentermine inhibit monoamine oxidase? Lancet. 1999 Apr 17;353(9161):1362-3. Pubmed
  2. Rothman RB: Is phentermine an inhibitor of monoamine oxidase? A critical appraisal. Synapse. 1999 May;32(2):141-5. Pubmed
  3. Ulus IH, Maher TJ, Wurtman RJ: Characterization of phentermine and related compounds as monoamine oxidase (MAO) inhibitors. Biochem Pharmacol. 2000 Jun 15;59(12):1611-21. Pubmed
  4. Kilpatrick IC, Traut M, Heal DJ: Monoamine oxidase inhibition is unlikely to be relevant to the risks associated with phentermine and fenfluramine: a comparison with their abilities to evoke monoamine release. Int J Obes Relat Metab Disord. 2001 Oct;25(10):1454-8. Pubmed
  5. Nandigama RK, Newton-Vinson P, Edmondson DE: Phentermine inhibition of recombinant human liver monoamine oxidases A and B. Biochem Pharmacol. 2002 Mar 1;63(5):865-9. Pubmed
Enzymes

1. Amine oxidase [flavin-containing] A

Actions: inhibitor

Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine

UniProt ID: P21397 Link_out
Gene: MAOA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nandigama RK, Newton-Vinson P, Edmondson DE: Phentermine inhibition of recombinant human liver monoamine oxidases A and B. Biochem Pharmacol. 2002 Mar 1;63(5):865-9. Pubmed
  2. Ulus IH, Maher TJ, Wurtman RJ: Characterization of phentermine and related compounds as monoamine oxidase (MAO) inhibitors. Biochem Pharmacol. 2000 Jun 15;59(12):1611-21. Pubmed

2. Amine oxidase [flavin-containing] B

Actions: inhibitor

Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine

UniProt ID: P27338 Link_out
Gene: MAOB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nandigama RK, Newton-Vinson P, Edmondson DE: Phentermine inhibition of recombinant human liver monoamine oxidases A and B. Biochem Pharmacol. 2002 Mar 1;63(5):865-9. Pubmed
  2. Ulus IH, Maher TJ, Wurtman RJ: Characterization of phentermine and related compounds as monoamine oxidase (MAO) inhibitors. Biochem Pharmacol. 2000 Jun 15;59(12):1611-21. Pubmed

3. Cytochrome P450 1A2

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. 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

4. Cytochrome P450 2C9

Actions: inhibitor, inducer

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

5. Cytochrome P450 2D6

Actions: 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. 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 July 25, 2011 11:34

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.