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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 Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Benzfetamine
Benzphetamine Hydrochloride
Benzylamphetamine
Salts Not Available
Brand names
Name Company
Didrex
Brand 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-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
Plain Text
IUPAC Name
benzyl(methyl)[(2S)-1-phenylpropan-2-yl]amine
SMILES
C[C@@H](CC1=CC=CC=C1)N(C)CC1=CC=CC=C1
Plain Text
Mass Spec show (8.86 KB)
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
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.
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
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 152-153 °C Not Available
water solubility Readily soluble Not Available
logP 4.1 Not Available
Predicted Properties
Property Value Source
water solubility 2.33e-02 g/l ALOGPS
logP 3.72 ALOGPS
logP 4.34 ChemAxon
logS -4 ALOGPS
pKa (strongest basic) 9.8 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 1 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 3.24 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 78.39 ChemAxon
polarizability 29.03 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C07538 Link_out
ChEBI 3044 Link_out
ChEMBL 3044 Link_out
Therapeutic Targets Database DAP001147 Link_out
PharmGKB PA448586 Link_out
RxList http://www.rxlist.com/cgi/generic/benzphet.htm Link_out
Drugs.com http://www.drugs.com/cdi/benzphetamine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Benzphetamine Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (16.6 KB)
Interactions
Drug Interactions
Drug Interaction
Chlorpromazine Antipsychotics 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.
Fluoxetine Amphetamines 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.
Fluphenazine Antipsychotics 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.
Fluvoxamine Amphetamines 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.
Guanethidine Benzphetamine may decrease the effect of guanethidine.
Isocarboxazid MAO 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.
Mesoridazine Antipsychotics 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.
Methotrimeprazine Antipsychotics 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.
Paroxetine Amphetamines 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.
Perphenazine Antipsychotics 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.
Phenelzine MAO 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.
Prochlorperazine Antipsychotics 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.
Promethazine Antipsychotics 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.
Propericiazine Antipsychotics 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.
Rasagiline MAO 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 bicarbonate Alkalinizing 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.
Telithromycin Telithromycin 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.
Thioridazine Antipsychotics 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.
Tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trandolapril Benzphetamine may reduce the efficacy of Trandolapril.
Tranylcypromine The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the amphetamine, Benzphetamine. Concomitant therapy should be avoided.
Trifluoperazine Antipsychotics 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.
Triprolidine Triprolidine may reduce the sedative effect of the antihistamine, Benzphetamine.
Voriconazole Voriconazole, 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 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 Link_out
Gene: SLC18A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

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:
  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

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:
  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

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:
  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
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:
  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

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:
  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

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

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 February 08, 2013 16:19