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Identification
NamePhendimetrazine
Accession NumberDB01579
Typesmall molecule
Groupsapproved, illicit
Description

Phendimetrazine is a weight loss medication. Phendimetrazine is chemically related to amphetamines and is a Schedule III drug under the Convention on Psychotropic Substances. In the United States, phendimetrazine is a Schedule III controlled substance under the Uniform Controlled Substances Act of 1970.

Structure
Thumb
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
AdipostNot Available
BontrilNot Available
MelfiatNot Available
StatobexNot Available
Brand mixturesNot Available
Categories
CAS number634-03-7
WeightAverage: 191.2695
Monoisotopic: 191.131014171
Chemical FormulaC12H17NO
InChI KeyInChIKey=MFOCDFTXLCYLKU-UHFFFAOYSA-N
InChI
InChI=1S/C12H17NO/c1-10-12(14-9-8-13(10)2)11-6-4-3-5-7-11/h3-7,10,12H,8-9H2,1-2H3
IUPAC Name
3,4-dimethyl-2-phenylmorpholine
SMILES
CC1C(OCCN1C)C1=CC=CC=C1
Mass Specshow(8.7 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassOxazinanes
SubclassMorpholines
Direct parentPhenylmorpholines
Alternative parentsBenzene and Substituted Derivatives; Tertiary Amines; Dialkyl Ethers; Polyamines
Substituentsbenzene; tertiary amine; dialkyl ether; polyamine; ether; amine; organonitrogen compound
Classification descriptionThis compound belongs to the phenylmorpholines. These are aromatic compounds containing a morpholine ring and a benzene ring linked to each other through a CC or a CN bond.
Pharmacology
IndicationUsed in the management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction.
PharmacodynamicsPhendimetrazine is a phenylalkylamine sympathomimetic amine with pharmacological 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 has been demonstrated with all drugs of this class in which these phenomena have been looked for. Drugs of this class used in obesity are commonly known as ''anorectics or anorexigenics." It has not been established, however, that the action of such drugs in treating obesity is primarily one of appetite suppression. Other central nervous system actions or metabolic effects, may be involved.
Mechanism of actionPhendimetrazine may act in a similar way to amphetamines in that it activates the alpha-adrenergic system to induce an appetite suppressive and metabolic increase effect. The drug also acts as a norepinephrine-dopamine releasing agent (NDRA). It can bind to and reverse the NET.
AbsorptionPeak plasma levels occur within 1 to 3 hours. Absorption is usually complete by 4 to 6 hours.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Approximately 30% of a given dose of phendimetrazine is metabolized into phenmetrazine, which may account for part of its anorectic effect, and probably also influences abuse potential; individuals who metabolise a greater proportion of phendimetrazine into phenmetrazine are more likely to develop problems with dependence and addiction

SubstrateEnzymesProduct
Phendimetrazine
    PhenmetrazineDetails
    Route of eliminationThe major route of elimination is via the kidneys where most of the drug and metabolites are excreted.
    Half life19-24 hours
    ClearanceNot Available
    ToxicityAcute overdosage of phendimetrazine may manifest itself by the following signs and symptoms: unusual restlessness, confusion, belligerance, hallucinations, and panic states. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension, or hypotension and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Poisoning may result in convulsions, coma and death.
    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 + 0.9969
    Blood Brain Barrier + 0.9846
    Caco-2 permeable + 0.7977
    P-glycoprotein substrate Substrate 0.6041
    P-glycoprotein inhibitor I Non-inhibitor 0.6769
    P-glycoprotein inhibitor II Non-inhibitor 0.9583
    Renal organic cation transporter Inhibitor 0.643
    CYP450 2C9 substrate Non-substrate 0.8398
    CYP450 2D6 substrate Substrate 0.6133
    CYP450 3A4 substrate Substrate 0.6142
    CYP450 1A2 substrate Non-inhibitor 0.7819
    CYP450 2C9 substrate Non-inhibitor 0.9346
    CYP450 2D6 substrate Non-inhibitor 0.6649
    CYP450 2C19 substrate Non-inhibitor 0.6534
    CYP450 3A4 substrate Non-inhibitor 0.8458
    CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8231
    Ames test Non AMES toxic 0.8256
    Carcinogenicity Non-carcinogens 0.9313
    Biodegradation Not ready biodegradable 0.9087
    Rat acute toxicity 2.6514 LD50, mol/kg Not applicable
    hERG inhibition (predictor I) Weak inhibitor 0.7016
    hERG inhibition (predictor II) Non-inhibitor 0.7799
    Pharmacoeconomics
    Manufacturers
    • Valeant pharmaceuticals international
    • Numark laboratories inc
    • Dm graham laboratories inc
    • Sandoz inc
    • Shire richwood inc
    • Mm mast and co
    • Vitarine pharmaceuticals inc
    • Solvay pharmaceuticals
    • Teva pharmaceuticals usa inc
    • Ferndale laboratories inc
    • Abc holding corp
    • Camall co inc
    • Tg united labs llc
    • Private formulations inc
    • Forest pharmaceuticals inc
    • Actavis totowa llc
    • Barr laboratories inc
    • Inwood laboratories inc sub forest laboratories inc
    • Ivax pharmaceuticals inc
    • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
    • Kv pharmaceutical co
    • Manufacturing chemists inc
    • Mikart inc
    • Nexgen pharma inc
    • Usl pharma inc
    • Watson laboratories inc
    • Wyeth ayerst laboratories
    Packagers
    Dosage forms
    FormRouteStrength
    TabletOral
    Prices
    Unit descriptionCostUnit
    Bontril Slow Release 105 mg 24 Hour Capsule1.67USDcapsule
    Bontril sr 105 mg capsule1.1USDcapsule
    Phendimetrazine Tartrate 105 mg 24 Hour Capsule1.07USDcapsule
    Bontril pdm 35 mg tablet0.83USDtablet
    Bontril 105 mg capsule sa0.48USDcapsule
    Phendimetrazine Tartrate 35 mg tablet0.24USDtablet
    Phendimetrazine 35 mg tablet0.21USDtablet
    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
    PatentsNot Available
    Properties
    Statesolid
    Experimental Properties
    PropertyValueSource
    boiling point134.5 °C at 1.20E+01 mm HgNot Available
    Predicted Properties
    PropertyValueSource
    water solubility2.43e+00 g/lALOGPS
    logP2.01ALOGPS
    logP2.17ChemAxon
    logS-1.9ALOGPS
    pKa (strongest basic)7.28ChemAxon
    physiological charge1ChemAxon
    hydrogen acceptor count2ChemAxon
    hydrogen donor count0ChemAxon
    polar surface area12.47ChemAxon
    rotatable bond count1ChemAxon
    refractivity57.76ChemAxon
    polarizability21.99ChemAxon
    number of rings2ChemAxon
    bioavailability1ChemAxon
    rule of fiveYesChemAxon
    Ghose filterYesChemAxon
    Veber's ruleYesChemAxon
    MDDR-like ruleNoChemAxon
    Spectra
    SpectraNot Available
    References
    Synthesis ReferenceNot Available
    General ReferenceNot Available
    External Links
    ResourceLink
    KEGG CompoundC07904
    PubChem Compound12460
    PubChem Substance46506122
    ChemSpider11950
    Therapeutic Targets DatabaseDAP000574
    PharmGKBPA450902
    RxListhttp://www.rxlist.com/cgi/generic/phendime.htm
    Drugs.comhttp://www.drugs.com/phendimetrazine.html
    WikipediaPhendimetrazine
    ATC CodesNot Available
    AHFS CodesNot Available
    PDB EntriesNot Available
    FDA labelNot Available
    MSDSNot Available
    Interactions
    Drug Interactions
    Drug
    ChlorpromazineDecreased anorexic effect, may increases psychotic symptoms
    FluoxetineRisk of serotoninergic syndrome
    FluphenazineDecreased anorexic effect, may increase psychotic symptoms
    FluvoxamineRisk of serotoninergic syndrome
    GuanethidinePhendimetrazine may decrease the effect of guanethidine.
    IsocarboxazidPossible hypertensive crisis
    MesoridazineDecreased 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 pyschotic symptoms
    PromethazineDecreased anorexic effect, may increase pyschotic symptoms
    PropericiazineDecreased anorexic effect, may increase pyschotic symptoms
    RasagilinePossible hypertensive crisis
    ThioridazineDecreased anorexic effect, may increase psychotic symptoms
    TramadolIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
    TrandolaprilPhendimetrazine may reduce the efficacy of Trandolapril.
    TranylcypromineThe MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the amphetamine, Phendimetrazine. Concomitant therapy should be avoided.
    TrifluoperazineDecreased anorexic effect, may increase psychotic symptoms
    TriprolidineTriprolidine may reduce the sedative effect of the antihistamine, Phendimetrazine.
    Food InteractionsNot Available

    1. Alpha-1A adrenergic receptor

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: agonist

    Components

    Name UniProt ID Details
    Alpha-1A adrenergic receptor P35348 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. Bray GA: Drug Insight: appetite suppressants. Nat Clin Pract Gastroenterol Hepatol. 2005 Feb;2(2):89-95. Pubmed
    4. Bray GA: A concise review on the therapeutics of obesity. Nutrition. 2000 Oct;16(10):953-60. Pubmed
    5. Rothman RB, Baumann MH: Therapeutic potential of monoamine transporter substrates. Curr Top Med Chem. 2006;6(17):1845-59. Pubmed

    2. Sodium-dependent noradrenaline transporter

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: negative modulator

    Components

    Name UniProt ID Details
    Sodium-dependent noradrenaline transporter P23975 Details

    References:

    1. Rothman RB, Baumann MH: Therapeutic potential of monoamine transporter substrates. Curr Top Med Chem. 2006;6(17):1845-59. Pubmed

    3. Alpha-1B adrenergic receptor

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: agonist

    Components

    Name UniProt ID Details
    Alpha-1B adrenergic receptor P35368 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. Bray GA: Drug Insight: appetite suppressants. Nat Clin Pract Gastroenterol Hepatol. 2005 Feb;2(2):89-95. Pubmed
    4. Bray GA: A concise review on the therapeutics of obesity. Nutrition. 2000 Oct;16(10):953-60. Pubmed
    5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
    6. Rothman RB, Baumann MH: Therapeutic potential of monoamine transporter substrates. Curr Top Med Chem. 2006;6(17):1845-59. Pubmed

    Comments
    Drug created on August 29, 2007 08:52 / Updated on January 29, 2014 08:32