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Identification
Name Pentoxifylline
Accession Number DB00806 (APRD00121)
Type small molecule
Groups approved
Description

A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
EHT0201
Salts Not Available
Brand names
Name Company
Azupentat
Dimethyloxohexylxanthine
Durapental
Oxpentifylline
Pentoxifyllin
Pentoxil
Pentoxiphyllium
Pentoxyfylline
PENTOXYPHYLINE
Pentoxyphylline
Rentylin
Torental
Trental
Vazofirin
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Brand mixtures Not Available
Categories
  • Free Radical Scavengers
  • Vasodilator Agents
  • Platelet Aggregation Inhibitors
  • Phosphodiesterase Inhibitors
  • Radiation-Protective Agents
  • Hematologic Agents
  • Hemorrheologic Agents
CAS number 6493-05-6
Weight Average: 278.307
Monoisotopic: 278.137890462
Chemical Formula C13H18N4O3
InChI Key InChIKey=BYPFEZZEUUWMEJ-UHFFFAOYSA-N
InChI
InChI=1S/C13H18N4O3/c1-9(18)6-4-5-7-17-12(19)10-11(14-8-15(10)2)16(3)13(17)20/h8H,4-7H2,1-3H3
Plain Text
IUPAC Name
3,7-dimethyl-1-(5-oxohexyl)-2,3,6,7-tetrahydro-1H-purine-2,6-dione
SMILES
CN1C=NC2=C1C(=O)N(CCCCC(C)=O)C(=O)N2C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Xanthines
Substructures
  • Xanthines
  • Pyrimidines and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Cyanamides
  • Ketones
Pharmacology
Indication For the treatment of patients with intermittent lameness or immobility arising from chronic occlusive arterial disease of the limbs.
Pharmacodynamics Pentoxifylline, a synthetic dimethylxanthine derivative structurally related to theophylline and caffeine, is used in the treatment of peripheral vascular diseases and in the management of cerebrovascular insufficiency, sickle cell disease, and diabetic neuropathy.
Mechanism of action Pentoxifylline inhibits erythrocyte phosphodiesterase, resulting in an increase in erythrocyte cAMP activity. Subsequently, the erythrocyte membrane becomes more resistant to deformity. Along with erythrocyte activity, pentoxifylline also decreases blood viscosity by reducing plasma fibrinogen concentrations and increasing fibrinolytic activity. It is also a non selective adenosine receptor antagonist.
Absorption Not Available
Volume of distribution Not Available
Protein binding 70%
Metabolism
Not Available
Route of elimination Excretion is almost totally urinary; the main biotransformation product is Metabolite V. Essentially no parent drug is found in the urine.
Half life 0.4-0.8 hours
Clearance Not Available
Toxicity LD50=1385 mg/kg(orally in mice)
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Actavis elizabeth llc
  • Apotex inc
  • Biovail laboratories inc
  • Heritage pharmaceuticals inc
  • Impax laboratories inc
  • Mylan pharmaceuticals inc
  • Pliva inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Upsher smith laboratories inc
  • Sanofi aventis us llc
Packagers
Dosage forms
Form Route Strength
Tablet, extended release Oral
Prices
Unit description Cost Unit
TRENtal 400 mg Controlled Release Tabs 1.4 USD tab
Trental er 400 mg tablet 1.27 USD tablet
Pentoxifylline powder 0.91 USD g
Trental 400 mg Sustained-Release Tablet 0.88 USD tablet
Pentoxifylline 400 mg tablet sa 0.71 USD tablet
Pentoxifylline CR 400 mg Controlled Release Tabs 0.62 USD tab
Pentoxil 400 mg Controlled Release Tabs 0.62 USD tab
Pentoxil er 400 mg tablet 0.62 USD tablet
Pentoxifylline er 400 mg tablet 0.6 USD tablet
Apo-Pentoxifylline Sr 400 mg Sustained-Release Tablet 0.4 USD tablet
Nu-Pentoxifylline-Sr 400 mg Sustained-Release Tablet 0.4 USD tablet
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Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 105 °C Not Available
water solubility 7.7E+004 mg/L (at 25 °C) MERCK INDEX (1996)
logP 0.29 BIOBYTE (1995)
Predicted Properties
Property Value Source
water solubility 5.17e+00 g/l ALOGPS
logP 0.08 ALOGPS
logP 0.23 ChemAxon
logS -1.7 ALOGPS
pKa (strongest acidic) 19.64 ChemAxon
pKa (strongest basic) -0.93 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 75.51 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 73.52 ChemAxon
polarizability 29.27 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. : European Pentoxifylline Multi-Infarct Dementia Study. Eur Neurol. 1996;36(5):315-21. Pubmed
External Links
Resource Link
KEGG Drug D00501 Link_out
KEGG Compound C07424 Link_out
PubChem Compound 4740 Link_out
PubChem Substance 46505940 Link_out
ChemSpider 4578 Link_out
BindingDB 10850 Link_out
Therapeutic Targets Database DAP000048 Link_out
PharmGKB PA450864 Link_out
Drug Product Database 1968432 Link_out
RxList http://www.rxlist.com/cgi/generic/pentox.htm Link_out
Drugs.com http://www.drugs.com/cdi/pentoxifylline.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Pentoxifylline Link_out
ATC Codes
  • C04AD03
AHFS Codes
  • 20:24.00
PDB Entries Not Available
FDA label show (51.7 KB)
MSDS show (73.9 KB)
Interactions
Drug Interactions
Drug Interaction
Acenocoumarol Pentoxifylline may increase the anticoagulant effect of acenocoumarol.
Aminophylline Pentoxifylline may increase the effect and toxicity of aminophylline.
Anisindione Pentoxifylline may increase the anticoagulant effect of anisindione.
Dicumarol Pentoxifylline may increase the anticoagulant effect of dicumarol.
Dyphylline Pentoxifylline increases the effect and toxicity of theophylline
Oxtriphylline Pentoxifylline increases the effect and toxicity of theophylline
Theophylline Pentoxifylline increases the effect and toxicity of theophylline
Warfarin Pentoxifylline may increase the anticoagulant effect of warfarin.
Food Interactions
  • Take with food to reduce irritation. Limit caffeine intake.
Targets

1. cAMP-specific 3',5'-cyclic phosphodiesterase 4B

Pharmacological action: yes
Actions: inhibitor

May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents

Organism class: human
UniProt ID: Q07343 Link_out
Gene: PDE4B 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

2. Adenosine A1 receptor

Pharmacological action: yes
Actions: antagonist

Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P30542 Link_out
Gene: ADORA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Daly JW, Jacobson KA, Ukena D: Adenosine receptors: development of selective agonists and antagonists. Prog Clin Biol Res. 1987;230:41-63. Pubmed

3. cGMP-specific 3',5'-cyclic phosphodiesterase

Pharmacological action: yes
Actions: inhibitor

Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'- GMP

Organism class: human
UniProt ID: O76074 Link_out
Gene: PDE5A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. cAMP-specific 3',5'-cyclic phosphodiesterase 4A

Pharmacological action: yes
Actions: inhibitor

Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate

Organism class: human
UniProt ID: P27815 Link_out
Gene: PDE4A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

5. Adenosine A2a receptor

Pharmacological action: yes
Actions: antagonist

Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Organism class: human
UniProt ID: P29274 Link_out
Gene: ADORA2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kreth S, Ledderose C, Luchting B, Weis F, Thiel M: Immunomodulatory properties of pentoxifylline are mediated via adenosine-dependent pathways. Shock. 2010 Jul;34(1):10-6. Pubmed

6. 5'-nucleotidase

Pharmacological action: unknown
Actions: inhibitor

Hydrolyzes extracellular nucleotides into membrane permeable nucleosides

Organism class: human
UniProt ID: P21589 Link_out
Gene: NT5E Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Ustunsoy H, Sivrikoz MC, Tarakcioglu M, Bakir K, Guldur E, Celkan MA: The effects of pentoxifylline on the myocardial inflammation and ischemia-reperfusion injury during cardiopulmonary bypass. J Card Surg. 2006 Jan-Feb;21(1):57-61. Pubmed
Enzymes

1. Cytochrome P450 1A2

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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19