DrugBank: Benzphetamine (DB00865)

targets (4) enzymes (3)

Identification

Name

Benzphetamine

Accession Number

DB00865 (APRD00759)

Type

small molecule

Groups

illicit, approved

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Benzfetamine
Benzphetamine Hydrochloride
Benzylamphetamine

Brand names

Didrex

Brand name mixtures

Not Available

Categories

Adrenergic Agents
Dopamine Agents
Dopamine Uptake Inhibitors
Adrenergic Uptake Inhibitors
Central Nervous System Stimulants
Sympathomimetics
Central Nervous System Agents

CAS number

156-08-1

Weight

Average: 239.3553
Monoisotopic: 239.167399677

Chemical Formula

C₁₇H₂₁N

InChI Key

InChIKey=YXKTVDFXDRQTKV-UHFFFAOYSA-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

Plain Text

IUPAC Name

benzyl(methyl)(1-phenylpropan-2-yl)amine

SMILES

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

Plain Text

Mass Spec

show (8.9 KB)

Taxonomy

Kingdom

Organic

Classes

Phenethylamines
Amphetamines

Substructures

Benzene and Derivatives
Aliphatic and Aryl Amines
Phenethylamines
Aromatic compounds
Amphetamines

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

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.

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.

Enzyme	Metabolite	Reaction	K_m	V_max
NADPH--cytochrome P450 reductase		N-demethylation

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

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

Form	Route	Strength
Tablet	Oral

Prices

Unit description	Cost	Unit
Didrex 50 mg tablet	1.71 USD	tablet
Benzphetamine hcl 50 mg tablet	1.43 USD	tablet

Patents

Not Available

Properties

State

solid

Melting point

152-153 oC

Experimental Properties

Property	Value	Source
water solubility	Readily soluble	PhysProp
logP	4.1	PhysProp

Predicted Properties

Property	Value	Source
water solubility	2.33e-02 g/l	ALOGPS
logP	3.72	ALOGPS
logP	4.34	ChemAxon Molconvert
logS	-4.01	ALOGPS
pKa		ChemAxon Molconvert
hydrogen acceptor count	1	ChemAxon Molconvert
hydrogen donor count	0	ChemAxon Molconvert
polar surface area	3.24	ChemAxon Molconvert
rotatable bond count	5	ChemAxon Molconvert
refractivity	78.39	ChemAxon Molconvert
polarizability	29.14	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Compound	C07538
PubChem Compound	2341
PubChem Substance	46506102
ChemSpider	2251
ChEBI	3044
ChEMBL	3044
Therapeutic Targets Database	DAP001147
PharmGKB	PA448586
Drug Product Database	0
RxList	http://www.rxlist.com/cgi/generic/benzphet.htm
Drugs.com	http://www.drugs.com/cdi/benzphetamine.html
Wikipedia	http://en.wikipedia.org/wiki/Benzphetamine

ATC Codes

Not Available

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

show (16.6 KB)

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. Synaptic vesicular amine transporter Pharmacological action: yes Actions: inducer Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Requisite for vesicular amine storage prior to secretion via exocytosis Organism class: human UniProt ID: Q05940 Gene: SLC18A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 Pharmacological action: yes Actions: agonist 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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol Organism class: human UniProt ID: P08913 Gene: ADRA2A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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 Pharmacological action: yes Actions: agonist 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) proteins Organism class: human UniProt ID: P35348 Gene: ADRA1A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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 Pharmacological action: unknown Actions: inhibitor Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals Organism class: human UniProt ID: Q01959 Gene: SLC6A3 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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

Targets

1. Synaptic vesicular amine transporter

Pharmacological action: yes
Actions: inducer

Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Requisite for vesicular amine storage prior to secretion via exocytosis

Organism class: human
UniProt ID: Q05940 Link_out

Gene: SLC18A2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Pharmacological action: yes
Actions: agonist

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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol

Organism class: human
UniProt ID: P08913 Link_out

Gene: ADRA2A Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Pharmacological action: yes
Actions: agonist

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) proteins

Organism class: human
UniProt ID: P35348 Link_out

Gene: ADRA1A Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Pharmacological action: unknown
Actions: inhibitor

Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: Q01959 Link_out

Gene: SLC6A3 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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

Enzymes
1. Cytochrome P450 3A4 Actions: substrate 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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide UniProt ID: P08684 Gene: CYP3A4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 Actions: substrate 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 unrelated compounds, including steroids, fatty acids, and xenobiotics UniProt ID: P20813 Gene: CYP2B6 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 Actions: substrate 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 UniProt ID: P16435 Gene: POR Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 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 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

Enzymes

1. Cytochrome P450 3A4

Actions: substrate

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out

Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Actions: substrate

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 unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20813 Link_out

Gene: CYP2B6 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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

Actions: substrate

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

UniProt ID: P16435 Link_out

Gene: POR

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
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
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
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 June 03, 2011 13:48

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.