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Identification
NameBenzphetamine
Accession NumberDB00865  (APRD00759)
Typesmall molecule
Groupsapproved, illicit
Description

A sympathomimetic agent with properties similar to dextroamphetamine. It is used in the treatment of obesity. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1222)

Structure
Thumb
Synonyms
SynonymLanguageCode
(+)-benzphetamineNot AvailableNot Available
(+)-N-benzyl-N,α-dimethylphenethylamineNot AvailableNot Available
(+)-N,α-dimethyl-N-(phenylmethyl)-benzeneethanamineNot AvailableNot Available
(S)-(+)-benzphetamineNot AvailableNot Available
(S)-(+)-N-benzyl-N,α-dimethylphenethylamineNot AvailableNot Available
(S)-benzphetamineNot AvailableNot Available
BenzaphetamineNot AvailableNot Available
BenzfetamineNot AvailableINN
BenzylamphetamineNot AvailableNot Available
d-N-methyl-N-benzyl-β-phenylisopropylamineNot AvailableNot Available
N-methyl-1-phenyl-N-(phenylmethyl)propan-2-amineNot AvailableNot Available
Salts
Name/CAS Structure Properties
Benzphetamine Hydrochloride
Thumb
  • InChI Key: ANFSNXAXVLRZCG-UHFFFAOYNA-N
  • Monoisotopic Mass: 275.144077416
  • Average Mass: 275.816
DBSALT000832
Brand names
NameCompany
DidrexPharmacia & Upjohn
Brand mixturesNot Available
Categories
CAS number156-08-1
WeightAverage: 239.3553
Monoisotopic: 239.167399677
Chemical FormulaC17H21N
InChI KeyInChIKey=YXKTVDFXDRQTKV-HNNXBMFYSA-N
InChI
InChI=1S/C17H21N/c1-15(13-16-9-5-3-6-10-16)18(2)14-17-11-7-4-8-12-17/h3-12,15H,13-14H2,1-2H3/t15-/m0/s1
IUPAC Name
benzyl(methyl)[(2S)-1-phenylpropan-2-yl]amine
SMILES
C[C@@H](CC1=CC=CC=C1)N(C)CC1=CC=CC=C1
Mass Specshow(8.86 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenethylamines
Direct parentAmphetamines and Derivatives
Alternative parentsTertiary Amines; Polyamines
Substituentstertiary amine; polyamine; 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 management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction
PharmacodynamicsBenzphetamine, a phenylalkylamin, is related to amphetamine both chemically and pharmacologically. It is an anorectic agent indicated in the management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction. Benzphetamine 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 actionAlthough the mechanism of action of the sympathomimetic appetite suppressants in the treatment of obesity is not fully known, these medications have pharmacological effects similar to those of amphetamines. Amphetamine and related sympathomimetic medications (such as benzphetamine) are thought to stimulate the release of norepinephrine and/or dopamine from storage sites in nerve terminals in the lateral hypothalamic feeding center, thereby producing a decrease in appetite. This release is mediated by the binding of benzphetamine to centrally located adrenergic receptors.
AbsorptionReadily absorbed from the gastro-intestinal tract and buccal mucosa. It Is resistant to metabolism by monoamine oxidase.
Volume of distributionNot Available
Protein binding75-99%
Metabolism

Hepatic. Benzphetamine's metabolites include amphetamine and methamphetamine.

SubstrateEnzymesProduct
Benzphetamine
    AmphetamineDetails
    Benzphetamine
      MethamphetamineDetails
      Route of eliminationNot Available
      Half life16 to 31 hours
      ClearanceNot Available
      ToxicityLD50=160 mg/kg (orally in rats). Acute overdosage may result in restlessness, tremor, tachypnea, confusion, assaultiveness, and panic states.
      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 + 0.9933
      Blood Brain Barrier + 0.9864
      Caco-2 permeable + 0.8815
      P-glycoprotein substrate Substrate 0.541
      P-glycoprotein inhibitor I Non-inhibitor 0.8803
      P-glycoprotein inhibitor II Non-inhibitor 0.9437
      Renal organic cation transporter Inhibitor 0.7013
      CYP450 2C9 substrate Non-substrate 0.769
      CYP450 2D6 substrate Non-substrate 0.588
      CYP450 3A4 substrate Non-substrate 0.5135
      CYP450 1A2 substrate Inhibitor 0.8684
      CYP450 2C9 substrate Non-inhibitor 0.9146
      CYP450 2D6 substrate Inhibitor 0.539
      CYP450 2C19 substrate Non-inhibitor 0.5997
      CYP450 3A4 substrate Non-inhibitor 0.8789
      CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8047
      Ames test Non AMES toxic 0.888
      Carcinogenicity Non-carcinogens 0.6584
      Biodegradation Not ready biodegradable 0.9825
      Rat acute toxicity 3.1442 LD50, mol/kg Not applicable
      hERG inhibition (predictor I) Weak inhibitor 0.8779
      hERG inhibition (predictor II) Non-inhibitor 0.5331
      Pharmacoeconomics
      Manufacturers
      • Corepharma llc
      • Impax laboratories inc
      • Kvk tech inc
      • Paddock laboratories inc
      • Tedor pharma inc
      • Tyco healthcare mallinckrodt
      • Pharmacia and upjohn co
      Packagers
      Dosage forms
      FormRouteStrength
      TabletOral
      Prices
      Unit descriptionCostUnit
      Didrex 50 mg tablet1.71USDtablet
      Benzphetamine hcl 50 mg tablet1.43USDtablet
      DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
      PatentsNot Available
      Properties
      Statesolid
      Experimental Properties
      PropertyValueSource
      melting point129-130Heinzelman, R.V. and Aspergren, B.D.; US. Patent 2,789,138; April 16,1957; assigned to The Upjohn Company.
      water solubilityReadily solubleNot Available
      logP4.1Not Available
      Predicted Properties
      PropertyValueSource
      water solubility2.33e-02 g/lALOGPS
      logP3.72ALOGPS
      logP4.34ChemAxon
      logS-4ALOGPS
      pKa (strongest basic)9.8ChemAxon
      physiological charge1ChemAxon
      hydrogen acceptor count1ChemAxon
      hydrogen donor count0ChemAxon
      polar surface area3.24ChemAxon
      rotatable bond count5ChemAxon
      refractivity78.39ChemAxon
      polarizability29.03ChemAxon
      number of rings2ChemAxon
      bioavailability1ChemAxon
      rule of fiveYesChemAxon
      Ghose filterYesChemAxon
      Veber's ruleYesChemAxon
      MDDR-like ruleNoChemAxon
      Spectra
      SpectraNot Available
      References
      Synthesis Reference

      Dennis J. Kalota, Keith G. Tomazi, “Crystallization Method for Benzphetamine.” U.S. Patent US20080262268, issued October 23, 2008.

      US20080262268
      General ReferenceNot Available
      External Links
      ResourceLink
      KEGG CompoundC07538
      ChEBI3044
      ChEMBLCHEMBL1201358
      Therapeutic Targets DatabaseDAP001147
      PharmGKBPA448586
      RxListhttp://www.rxlist.com/cgi/generic/benzphet.htm
      Drugs.comhttp://www.drugs.com/cdi/benzphetamine.html
      WikipediaBenzphetamine
      ATC CodesNot Available
      AHFS CodesNot Available
      PDB EntriesNot Available
      FDA labelNot Available
      MSDSshow(16.6 KB)
      Interactions
      Drug Interactions
      Drug
      ChlorpromazineAntipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.
      FluoxetineAmphetamines may enhance the adverse/toxic effect of Serotonin Modulators. The risk of serotonin syndrome may be increased. Monitor patients closely for signs and symptoms of serotonin syndrome (e.g., agitation, tremor, tachycardia, etc.) when using amphetamines and serotonin modulators in combination.
      FluphenazineAntipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.
      FluvoxamineAmphetamines may enhance the adverse/toxic effect of Serotonin Modulators. The risk of serotonin syndrome may be increased. Monitor patients closely for signs and symptoms of serotonin syndrome (e.g., agitation, tremor, tachycardia, etc.) when using amphetamines and serotonin modulators in combination.
      GuanethidineBenzphetamine may decrease the effect of guanethidine.
      IsocarboxazidMAO Inhibitors may enhance the hypertensive effect of Amphetamines. Concomitant use of amphetamines and monoamine oxidase inhibitors (MAOI) should be avoided. If used concomitantly, careful monitoring of blood pressure must occur. It may take up to 2 weeks after the discontinuation of an MAOI for the effects to dissipate enough to afford safety to the administration of interacting agents.
      MesoridazineAntipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.
      MethotrimeprazineAntipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.
      ParoxetineAmphetamines may enhance the adverse/toxic effect of Serotonin Modulators. The risk of serotonin syndrome may be increased. Monitor patients closely for signs and symptoms of serotonin syndrome (e.g., agitation, tremor, tachycardia, etc.) when using amphetamines and serotonin modulators in combination.
      PerphenazineAntipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.
      PhenelzineMAO Inhibitors may enhance the hypertensive effect of Amphetamines. Concomitant use of amphetamines and monoamine oxidase inhibitors (MAOI) should be avoided. If used concomitantly, careful monitoring of blood pressure must occur. It may take up to 2 weeks after the discontinuation of an MAOI for the effects to dissipate enough to afford safety to the administration of interacting agents.
      ProchlorperazineAntipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.
      PromethazineAntipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.
      PropericiazineAntipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.
      RasagilineMAO Inhibitors may enhance the hypertensive effect of Amphetamines. Concomitant use of amphetamines and monoamine oxidase inhibitors (MAOI) should be avoided. If used concomitantly, careful monitoring of blood pressure must occur. It may take up to 2 weeks after the discontinuation of an MAOI for the effects to dissipate enough to afford safety to the administration of interacting agents.
      Sodium bicarbonateAlkalinizing agents such as sodium bicarbonate may decrease the excretion of amphetamines like benzphetamine. Increased clinical effects and/or toxicity may occur. Therapy modification should be considered.
      TelithromycinTelithromycin may reduce clearance of Benzphetamine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Benzphetamine if Telithromycin is initiated, discontinued or dose changed.
      ThioridazineAntipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.
      TramadolIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
      TrandolaprilBenzphetamine may reduce the efficacy of Trandolapril.
      TranylcypromineThe MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the amphetamine, Benzphetamine. Concomitant therapy should be avoided.
      TrifluoperazineAntipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.
      TriprolidineTriprolidine may reduce the sedative effect of the antihistamine, Benzphetamine.
      VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of benzphetamine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of benzphetamine if voriconazole is initiated, discontinued or dose changed.
      Food InteractionsNot Available

      1. Synaptic vesicular amine transporter

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: inducer

      Components

      Name UniProt ID Details
      Synaptic vesicular amine transporter Q05940 Details

      References:

      1. Sulzer D, Chen TK, Lau YY, Kristensen H, Rayport S, Ewing A: Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport. J Neurosci. 1995 May;15(5 Pt 2):4102-8. Pubmed

      2. Alpha-2A adrenergic receptor

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: agonist

      Components

      Name UniProt ID Details
      Alpha-2A adrenergic receptor P08913 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. 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

      4. Sodium-dependent dopamine transporter

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Sodium-dependent dopamine transporter Q01959 Details

      References:

      1. Sulzer D, Sonders MS, Poulsen NW, Galli A: Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol. 2005 Apr;75(6):406-33. Pubmed
      2. Kahlig KM, Binda F, Khoshbouei H, Blakely RD, McMahon DG, Javitch JA, Galli A: Amphetamine induces dopamine efflux through a dopamine transporter channel. Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3495-500. Epub 2005 Feb 22. Pubmed

      1. Cytochrome P450 3A4

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 3A4 P08684 Details

      References:

      1. Seree EJ, Pisano PJ, Placidi M, Rahmani R, Barra YA: Identification of the human and animal hepatic cytochromes P450 involved in clonazepam metabolism. Fundam Clin Pharmacol. 1993;7(2):69-75. Pubmed

      2. Cytochrome P450 2B6

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 2B6 P20813 Details

      References:

      1. Bumpus NN, Sridar C, Kent UM, Hollenberg PF: The naturally occurring cytochrome P450 (P450) 2B6 K262R mutant of P450 2B6 exhibits alterations in substrate metabolism and inactivation. Drug Metab Dispos. 2005 Jun;33(6):795-802. Epub 2005 Mar 15. Pubmed
      2. Shebley M, Kent UM, Ballou DP, Hollenberg PF: Mechanistic analysis of the inactivation of cytochrome P450 2B6 by phencyclidine: effects on substrate binding, electron transfer, and uncoupling. Drug Metab Dispos. 2009 Apr;37(4):745-52. Epub 2009 Jan 14. Pubmed

      3. NADPH--cytochrome P450 reductase

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      NADPH--cytochrome P450 reductase P16435 Details

      References:

      1. Kanaeva IP, Nikityuk OV, Davydov DR, Dedinskii IR, Koen YM, Kuznetsova GP, Skotselyas ED, Bachmanova GI, Archakov AI: Comparative study of monomeric reconstituted and membrane microsomal monooxygenase systems of the rabbit liver. II. Kinetic parameters of reductase and monooxygenase reactions. Arch Biochem Biophys. 1992 Nov 1;298(2):403-12. Pubmed
      2. Matsumoto T, Emi Y, Kawabata S, Omura T: Purification and characterization of three male-specific and one female-specific forms of cytochrome P-450 from rat liver microsomes. J Biochem (Tokyo). 1986 Nov;100(5):1359-71. Pubmed
      3. Kojima H, Takahashi K, Sakane F, Koyama J: Purification and characterization of NADPH-cytochrome c reductase from porcine polymorphonuclear leukocytes. J Biochem (Tokyo). 1987 Nov;102(5):1083-8. Pubmed
      4. Dutton DR, McMillen SK, Parkinson A: Purification of rat liver microsomal cytochrome P-450b without the use of nonionic detergent. J Biochem Toxicol. 1988 Summer;3:131-45. Pubmed
      5. Halpert JR, Miller NE, Gorsky LD: On the mechanism of the inactivation of the major phenobarbital-inducible isozyme of rat liver cytochrome P-450 by chloramphenicol. J Biol Chem. 1985 Jul 15;260(14):8397-403. Pubmed

      Comments
      Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12