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Identification
NamePhentermine
Accession NumberDB00191  (APRD00093)
Typesmall molecule
Groupsapproved, illicit
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]. Some common brand names for phentermine are Adipex-P® and Suprenza™. Phentermine is also available in combination medications such as Qsymia®.

Structure
Thumb
Synonyms
SynonymLanguageCode
alpha,alpha-DimethylphenethylamineNot AvailableNot Available
Salts
Name/CAS Structure Properties
Phentermine Hydrochloride
1197-21-3
Thumb
  • InChI Key: NCAIGTHBQTXTLR-UHFFFAOYSA-N
  • Monoisotopic Mass: 185.097127224
  • Average Mass: 185.694
DBSALT000138
Brand names
NameCompany
Adipex-PNot Available
DuromineNot Available
FastinNot Available
IonaminNot Available
ObenixNot Available
Obestin-30Not Available
PhentercotNot Available
PhentrideNot Available
Pro-FastNot Available
SuprenzaCITIUS PHARMS
TeramineNot Available
ZantrylNot Available
Brand mixtures
Brand NameIngredients
Fen-phenfenfluramine + phentermine
Qsymiaphentermine + topiramate extended-release
Categories
CAS number122-09-8
WeightAverage: 149.2328
Monoisotopic: 149.120449485
Chemical FormulaC10H15N
InChI KeyInChIKey=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
IUPAC Name
2-methyl-1-phenylpropan-2-amine
SMILES
CC(C)(N)CC1=CC=CC=C1
Mass Specshow(7.33 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenethylamines
Direct parentAmphetamines and Derivatives
Alternative parentsPolyamines; Monoalkylamines
Substituentspolyamine; primary amine; primary aliphatic amine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.
Pharmacology
IndicationFor the treatment and management of obesity.
PharmacodynamicsPhentermine 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 actionPhentermine 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.
AbsorptionPhentermine is rapidly absorbed after oral ingestion.
Volume of distributionNot Available
Protein bindingApproximately 96.3%
Metabolism

Hepatic.

Route of eliminationNot Available
Half life16 to 31 hours
ClearanceNot Available
ToxicityLD50 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9964
Blood Brain Barrier + 0.959
Caco-2 permeable + 0.7688
P-glycoprotein substrate Non-substrate 0.6477
P-glycoprotein inhibitor I Non-inhibitor 0.934
P-glycoprotein inhibitor II Non-inhibitor 0.9801
Renal organic cation transporter Non-inhibitor 0.8236
CYP450 2C9 substrate Non-substrate 0.8411
CYP450 2D6 substrate Substrate 0.7204
CYP450 3A4 substrate Non-substrate 0.6493
CYP450 1A2 substrate Non-inhibitor 0.7962
CYP450 2C9 substrate Non-inhibitor 0.8861
CYP450 2D6 substrate Inhibitor 0.7825
CYP450 2C19 substrate Non-inhibitor 0.8996
CYP450 3A4 substrate Non-inhibitor 0.7348
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8782
Ames test Non AMES toxic 0.9681
Carcinogenicity Non-carcinogens 0.6949
Biodegradation Not ready biodegradable 0.9303
Rat acute toxicity 2.8400 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9867
hERG inhibition (predictor II) Non-inhibitor 0.8734
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
FormRouteStrength
CapsuleOral
CapsuleOral11.25 mg/69 mg (PHENTERMINE HYDROCHLORIDE/ TOPIRAMATE ER)
CapsuleOral15 mg/92 mg (PHENTERMINE HYDROCHLORIDE/ TOPIRAMATE ER)
CapsuleOral3.75 mg/23 mg (PHENTERMINE HYDROCHLORIDE/ TOPIRAMATE ER)
CapsuleOral7.5 mg/46 mg (PHENTERMINE HYDROCHLORIDE/ TOPIRAMATE ER)
Prices
Unit descriptionCostUnit
Phentermine hcl powder10.71USDg
Ionamin 30 mg capsule sa2.87USDcapsule
Adipex-P 37.5 mg capsule2.2USDcapsule
Adipex-p 37.5 mg tablet2.15USDtablet
Phentermine 37.5 mg tablet1.54USDtablet
Phentermine HCl 15 mg capsule1.18USDcapsule
Phentermine HCl 30 mg capsule1.17USDcapsule
Ionamin 15 mg capsule sa1.15USDcapsule
Phentermine HCl 37.5 mg capsule1.0USDcapsule
Phentermine HCl 37.5 mg tablet1.0USDtablet
Phentermine 8 mg tablet0.54USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point205 °CNot Available
water solubility18.6 g/LNot Available
logP1.90HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility7.57e-01 g/lALOGPS
logP2.32ALOGPS
logP2.08ChemAxon
logS-2.3ALOGPS
pKa (strongest basic)10.25ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count1ChemAxon
hydrogen donor count1ChemAxon
polar surface area26.02ChemAxon
rotatable bond count2ChemAxon
refractivity48.34ChemAxon
polarizability17.87ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot 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
ResourceLink
KEGG DrugD05458
KEGG CompoundC07438
PubChem Compound4771
PubChem Substance46508515
ChemSpider4607
ChEBI8080
ChEMBLCHEMBL1574
Therapeutic Targets DatabaseDAP000719
PharmGKBPA164748099
Drug Product Database891770
RxListhttp://www.rxlist.com/cgi/generic/phenterm.htm
Drugs.comhttp://www.drugs.com/phentermine.html
WikipediaPhentermine
ATC CodesA08AA01
AHFS Codes
  • 28:20.92
PDB EntriesNot Available
FDA labelshow(159 KB)
MSDSshow(48.2 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
GuanethidinePhentermine may decrease the effect of guanethidine.
IsocarboxazidPossible 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 psychotic 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
TramadolIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TrandolaprilPhentermine may reduce the efficacy of Trandolapril.
TranylcypromineThe MAO inhibitor, tranylcypromine, may increase the vasopressor effect of the amphetamine, phentermine. Concomitant therapy should be avoided.
TrifluoperazineDecreased anorexic effect, may increase psychotic symptoms
TriflupromazineDecreased anorexic effect, may increase psychotic symptoms
TriprolidineTriprolidine may reduce the sedative effect of the antihistamine, Phentermine.
VenlafaxineRisk of serotoninergic syndrome
Food Interactions
  • Limit caffeine intake.
  • Take without regard to meals.

1. Sodium-dependent noradrenaline transporter

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent noradrenaline transporter P23975 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent serotonin transporter P31645 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent dopamine transporter Q01959 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Amine oxidase [flavin-containing] A P21397 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Amine oxidase [flavin-containing] B P27338 Details

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

1. Amine oxidase [flavin-containing] A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Amine oxidase [flavin-containing] A P21397 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Amine oxidase [flavin-containing] B P27338 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: 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

4. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor inducer

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

5. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 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

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08