Identification

Name
Benzphetamine
Accession Number
DB00865  (APRD00759)
Type
Small Molecule
Groups
Approved, 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
  • (+)-benzphetamine
  • (+)-N-Benzyl-N,alpha-dimethylphenethylamine
  • (+)-N-benzyl-N,α-dimethylphenethylamine
  • (+)-N,alpha-Dimethyl-N-(phenylmethyl)-benzeneethanamine
  • (+)-N,α-dimethyl-N-(phenylmethyl)-benzeneethanamine
  • (AlphaS)-N,alpha-dimethylphenethylamine
  • (S)-(+)-benzphetamine
  • (S)-(+)-N-Benzyl-N,alpha-dimethylphenethylamine
  • (S)-(+)-N-benzyl-N,α-dimethylphenethylamine
  • (S)-benzphetamine
  • Benzaphetamine
  • Benzfetamina
  • Benzfetamine
  • Benzfetaminum
  • Benzphetamine
  • Benzylamphetamine
  • D-N-Methyl-N-benzyl-beta-phenylisopropylamine
  • d-N-methyl-N-benzyl-β-phenylisopropylamine
  • N-methyl-1-phenyl-N-(phenylmethyl)propan-2-amine
Product Ingredients
IngredientUNIICASInChI Key
Benzphetamine Hydrochloride43DWT87QT75411-22-3ANFSNXAXVLRZCG-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DidrexTablet50 mg/1OralPharmacia & Upjohn Inc1960-10-262015-09-30Us
DidrexTablet50 mg/1OralA S Medication Solutions1960-10-26Not applicableUs
DidrexTablet50 mg/1OralPd Rx Pharmaceuticals, Inc.1960-10-262016-12-15Us
DidrexTablet50 mg/1OralA S Medication Solutions1960-10-26Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BenzphetamineTablet25 mg/1OralTedor Pharma Inc.2016-02-01Not applicableUs
Benzphetamine HydrochlorideTablet50 mg/1OralC.O. Truxton, Inc.2011-11-012013-10-17Us
Benzphetamine HydrochlorideTablet50 mg/1Oralbryant ranch prepack2010-07-21Not applicableUs
Benzphetamine HydrochlorideTablet50 mg/1OralSolco healthcare U.S., LLC2011-08-01Not applicableUs
Benzphetamine HydrochlorideTablet50 mg/1OralImpax Generics2008-12-012010-04-30Us
Benzphetamine HydrochlorideTablet25 mg/1OralNivagen Pharmaceuticals, Inc.2016-01-15Not applicableUs
Benzphetamine HydrochlorideTablet50 mg/1Oralbryant ranch prepack2016-01-15Not applicableUs
Benzphetamine HydrochlorideTablet50 mg/1OralPd Rx Pharmaceuticals, Inc.2010-07-21Not applicableUs
Benzphetamine HydrochlorideTablet, coated50 mg/1OralCore Pharma, Llc2009-01-162011-03-31Us
Benzphetamine HydrochlorideTablet50 mg/1OralBoca Pharmacal, Inc.2010-09-072018-09-30Us
Categories
UNII
0M3S43XK27
CAS number
156-08-1
Weight
Average: 239.3553
Monoisotopic: 239.167399677
Chemical Formula
C17H21N
InChI Key
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

Pharmacology

Indication

For the management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction

Associated Conditions
Pharmacodynamics

Benzphetamine, 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 action

Although 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.

TargetActionsOrganism
ASynaptic vesicular amine transporter
inducer
Human
AAlpha-2A adrenergic receptor
agonist
Human
AAlpha-1A adrenergic receptor
agonist
Human
USodium-dependent dopamine transporter
inhibitor
Human
Absorption

Readily absorbed from the gastro-intestinal tract and buccal mucosa. It Is resistant to metabolism by monoamine oxidase.

Volume of distribution
Not Available
Protein binding

75-99%

Metabolism

Hepatic. Benzphetamine's metabolites include amphetamine and methamphetamine.

Route of elimination
Not Available
Half life

16 to 31 hours

Clearance
Not Available
Toxicity

LD50=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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Benzphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Benzphetamine.
3-isobutyl-1-methyl-7H-xanthineThe risk or severity of adverse effects can be increased when Benzphetamine is combined with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when 3,4-Methylenedioxyamphetamine is combined with Benzphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Benzphetamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Benzphetamine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of serotonin syndrome can be increased when 5-methoxy-N,N-dimethyltryptamine is combined with Benzphetamine.
6-O-benzylguanineThe risk or severity of adverse effects can be increased when Benzphetamine is combined with 6-O-benzylguanine.
7-DeazaguanineThe risk or severity of adverse effects can be increased when Benzphetamine is combined with 7-Deazaguanine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Benzphetamine.
Food Interactions
Not Available

References

Synthesis Reference

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

US20080262268
General References
Not Available
External Links
Human Metabolome Database
HMDB0015003
KEGG Compound
C07538
PubChem Compound
5311017
PubChem Substance
46506102
ChemSpider
4470556
ChEBI
3044
ChEMBL
CHEMBL3545985
Therapeutic Targets Database
DAP001147
PharmGKB
PA448586
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Benzphetamine
MSDS
Download (16.6 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Corepharma llc
  • Impax laboratories inc
  • Kvk tech inc
  • Paddock laboratories inc
  • Tedor pharma inc
  • Tyco healthcare mallinckrodt
  • Pharmacia and upjohn co
Packagers
  • Aidarex Pharmacuticals LLC
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Boca Pharmacal
  • Chattem Chemicals Inc.
  • Corepharma LLC
  • Dispensing Solutions
  • Global Pharmaceuticals
  • Impax Laboratories Inc.
  • KVK-Tech Inc.
  • Metrics Inc.
  • Nucare Pharmaceuticals Inc.
  • Paddock Labs
  • Patheon Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmacia Inc.
  • Prepak Systems Inc.
  • Rising Pharmaceuticals
  • Tedor Pharma Inc.
Dosage forms
FormRouteStrength
TabletOral50 mg/1
Tablet, coatedOral50 mg/1
Tablet, film coatedOral50 mg/1
TabletOral25 mg/1
Prices
Unit descriptionCostUnit
Didrex 50 mg tablet1.71USD tablet
Benzphetamine hcl 50 mg tablet1.43USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)129-130Heinzelman, 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 Solubility0.0233 mg/mLALOGPS
logP3.72ALOGPS
logP4.34ChemAxon
logS-4ALOGPS
pKa (Strongest Basic)9.8ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area3.24 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity78.39 m3·mol-1ChemAxon
Polarizability29.03 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9933
Blood Brain Barrier+0.9864
Caco-2 permeable+0.8815
P-glycoprotein substrateSubstrate0.541
P-glycoprotein inhibitor INon-inhibitor0.8803
P-glycoprotein inhibitor IINon-inhibitor0.9437
Renal organic cation transporterInhibitor0.7013
CYP450 2C9 substrateNon-substrate0.769
CYP450 2D6 substrateNon-substrate0.588
CYP450 3A4 substrateNon-substrate0.5135
CYP450 1A2 substrateInhibitor0.8684
CYP450 2C9 inhibitorNon-inhibitor0.9146
CYP450 2D6 inhibitorInhibitor0.539
CYP450 2C19 inhibitorNon-inhibitor0.5997
CYP450 3A4 inhibitorNon-inhibitor0.8789
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8047
Ames testNon AMES toxic0.888
CarcinogenicityNon-carcinogens0.6584
BiodegradationNot ready biodegradable0.9825
Rat acute toxicity3.1442 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8779
hERG inhibition (predictor II)Non-inhibitor0.5331
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (8.86 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound 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
Phenylpropanes / Phenylmethylamines / Benzylamines / Aralkylamines / Trialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Amphetamine or derivatives / Phenylpropane / Phenylmethylamine / Benzylamine / Aralkylamine / Tertiary aliphatic amine / Tertiary amine / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
tertiary amine, amphetamines (CHEBI:3044)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inducer
General Function
Monoamine transmembrane transporter activity
Specific Function
Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles...
Gene Name
SLC18A2
Uniprot ID
Q05940
Uniprot Name
Synaptic vesicular amine transporter
Molecular Weight
55712.075 Da
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:7751968]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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
Uniprot Name
Sodium-dependent dopamine transporter
Molecular Weight
68494.255 Da
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:15955613]
  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:15728379]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
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:8486332]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
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 un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
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:15769884]
  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. doi: 10.1124/dmd.108.024661. Epub 2009 Jan 14. [PubMed:19144770]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
Specific Function
This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.
Gene Name
POR
Uniprot ID
P16435
Uniprot Name
NADPH--cytochrome P450 reductase
Molecular Weight
76689.12 Da
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:1416971]
  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. 1986 Nov;100(5):1359-71. [PubMed:2434473]
  3. Kojima H, Takahashi K, Sakane F, Koyama J: Purification and characterization of NADPH-cytochrome c reductase from porcine polymorphonuclear leukocytes. J Biochem. 1987 Nov;102(5):1083-8. [PubMed:3125159]
  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:3148724]
  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:3924914]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 07:44