T3DB: Phentermine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (6)XML

Targets (6)

Record Information

Version

2.0

Creation Date

2009-07-21 20:26:15 UTC

Update Date

2014-12-24 20:25:50 UTC

Accession Number

T3D2709

Identification

Common Name

Phentermine

Class

Small Molecule

Description

Phentermine is only found in individuals that have used or taken this drug. It is 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. 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.

Compound Type

Adrenergic Agent
Amine
Anorexigenic Agent
Appetite Depressant
Central Nervous System Agent
Central Nervous System Stimulant
Drug
Metabolite
Organic Compound
Stimulant
Sympathomimetic
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(alpha,alpha)-Dimethylphenethylamine
Adipex-P
alpha,alpha-Dimethylphenethylamine
Duromine
Fastin
Fentermina
Ionamin
Obenix
Obestin-30
Phentercot
Phenterminum
Phentride
Pro-Fast
Suprenza
Teramine
Zantryl

Chemical Formula

C₁₀H₁₅N

Average Molecular Mass

149.233 g/mol

Monoisotopic Mass

149.120 g/mol

CAS Registry Number

122-09-8

IUPAC Name

2-methyl-1-phenylpropan-2-amine

Traditional Name

phentermine

SMILES

CC(C)(N)CC1=CC=CC=C1

InChI Identifier

InChI=1S/C10H15N/c1-10(2,11)8-9-6-4-3-5-7-9/h3-7H,8,11H2,1-2H3

InChI Key

InChIKey=DHHVAGZRUROJKS-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Phenethylamines

Direct Parent

Amphetamines and derivatives

Alternative Parents

Substituents

Amphetamine or derivatives
Phenylpropane
Aralkylamine
Organic nitrogen compound
Organopnictogen compound
Hydrocarbon derivative
Primary amine
Organonitrogen compound
Primary aliphatic amine
Amine
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

primary amine (CHEBI:8080 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	205°C
Boiling Point	Not Available
Solubility	18.6 g/L
LogP	1.9

Predicted Properties

Property	Value	Source
Water Solubility	0.76 g/L	ALOGPS
logP	2.32	ALOGPS
logP	2.08	ChemAxon
logS	-2.3	ALOGPS
pKa (Strongest Basic)	10.25	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	1	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	26.02 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	48.34 m³·mol⁻¹	ChemAxon
Polarizability	17.87 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a4l-9000000000-4b4613b0051412392011	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 80V, Positive	splash10-0006-9000000000-1317a1dff976bad4f840	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 45V, Positive	splash10-0006-9100000000-c3cf4661cf2e9753892b	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-0006-9000000000-798c9f163004230fe723	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Positive	splash10-00kf-9000000000-356c0f3eb16f8fe213c0	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-00kf-9000000000-12472f6717ab22723d53	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 15V, Positive	splash10-0006-9000000000-d5cc268e81c53c1db691	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9100000000-bfce4f0893d61e18c642	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 75V, Positive	splash10-0006-9000000000-4027bc21c9067b2afaaf	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 65V, Positive	splash10-0006-9000000000-78df824f14afb3ef5819	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-014l-9000000000-162a1d1b79c4d13aa4d0	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 45V, Positive	splash10-014l-9000000000-9d917981d06565d9120a	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 60V, Positive	splash10-014i-9000000000-2ee6ba63f942e329e01b	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 45V, Positive	splash10-014l-9000000000-87fec87ba12fab4c26b6	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 70V, Positive	splash10-0006-9000000000-6482075e713588714fc7	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 50V, Positive	splash10-0006-9000000000-a9d629ba954d37de1894	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 25V, Positive	splash10-0006-9000000000-2edf07337f14f6bb795a	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 80V, Positive	splash10-0006-9000000000-57fedb34031977b99d69	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-0006-9000000000-40c3cdc442be6ab34e41	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Positive	splash10-00dr-9200000000-e6e9a40aadab17c1eb7d	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0ue9-0900000000-f2eb273dfd0ec45869c5	2015-04-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0f89-2900000000-f527ee48b9e2784c178c	2015-04-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0159-4900000000-548f73a83354267c9f81	2015-04-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0002-0900000000-c7ab0aa268d14ae3da39	2015-04-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0002-1900000000-ce1c08c021fbc1cc5c8c	2015-04-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-001i-2900000000-94b2b38953d359938c0a	2015-04-25	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0a4i-9100000000-7037d3f1fad22de72c33	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 90 MHz, CDCl₃, experimental)	Not Available	2014-09-20	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 15.09 MHz, CDCl₃, experimental)	Not Available	2014-09-23	View Spectrum

Toxicity Profile

Route of Exposure

Phentermine is rapidly absorbed after oral ingestion.

Mechanism of Toxicity

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.

Metabolism

Hepatic. Half Life: 16 to 31 hours

Toxicity Values

LD50: 15 to 20 mg/kg (monkey).

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For the treatment and management of obesity.

Minimum Risk Level

Not Available

Health Effects

Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion. Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion.

Symptoms

Symptoms of overdose include delirium, mania, self-injury, marked hypertension, tachycardia, arrhythmia, hyperpyrexia, convulsion, coma, and circulatory collapse.

Treatment

Management of acute phentermine intoxication is largely symptomatic and includes lavage and sedation with a barbiturate. Acidification of the urine increases phentermine excretion. Intravenous phentolamine (REGITINE) has been suggested for possible acute, severe hypertension, if this complicates phentermine overdosage. (4)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

8080

BioCyc ID

CPD-7657

CTD ID

Not Available

Stitch ID

Phentermine

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Phentermine

References

Synthesis Reference

Not Available

MSDS

Link

General References

Bray GA: A concise review on the therapeutics of obesity. Nutrition. 2000 Oct;16(10):953-60. [11054601 ]
Nelson DL, Gehlert DR: Central nervous system biogenic amine targets for control of appetite and energy expenditure. Endocrine. 2006 Feb;29(1):49-60. [16622292 ]
Drugs.com [Link]
RxList: The Internet Drug Index (2009). [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Amine oxidase [flavin-containing] B

General Function:: Primary amine oxidase activity
Specific Function:: 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.
Gene Name:: MAOB
Uniprot ID:: P27338
Molecular Weight:: 58762.475 Da

References

Rothman RB: Is phentermine an inhibitor of monoamine oxidase? A critical appraisal. Synapse. 1999 May;32(2):141-5. [10231134 ]
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. [10799660 ]
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. [11673765 ]
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. [11911838 ]
Rothman RB: Does phentermine inhibit monoamine oxidase? Lancet. 1999 Apr 17;353(9161):1362-3. [10218558 ]

Target Details

2. Amine oxidase [flavin-containing] A

General Function:: Serotonin binding
Specific Function:: 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.
Gene Name:: MAOA
Uniprot ID:: P21397
Molecular Weight:: 59681.27 Da

References

Rothman RB: Is phentermine an inhibitor of monoamine oxidase? A critical appraisal. Synapse. 1999 May;32(2):141-5. [10231134 ]
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. [10799660 ]
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. [11673765 ]
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. [11911838 ]

Target Details

3. Sodium-dependent serotonin transporter

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

References

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. [17459426 ]
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. [14675103 ]
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. [16380550 ]
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. [10458725 ]

Target Details

4. Sodium-dependent noradrenaline transporter

General Function:: Norepinephrine:sodium symporter activity
Specific Function:: Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:: SLC6A2
Uniprot ID:: P23975
Molecular Weight:: 69331.42 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
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. [17016423 ]

Target Details

5. 5-hydroxytryptamine receptor 2B

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	>10 uM	Not Available	BindingDB 50246598

References

Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL: Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation. 2000 Dec 5;102(23):2836-41. [11104741 ]

Target Details

6. Sodium-dependent dopamine transporter

General Function:: Monoamine transmembrane transporter activity
Specific Function:: Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:: SLC6A3
Uniprot ID:: Q01959
Molecular Weight:: 68494.255 Da

References

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. [17459426 ]

Phentermine (T3D2709)

Structure for T3D2709: Phentermine

Targets

References

References

References

References

Binding/Activity Constants

References

References