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targets (4) transporters (3)
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Identification
Name Dipyridamole
Accession Number DB00975 (APRD00360)
Type small molecule
Groups approved
Description

A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Dipiridamol
  • Dipyridamine
  • Dipyridamol
  • Dipyudamine
  • Dypyridamol
  • Usaf Ge-12
Brand names
  • Aggrenox
  • Agilease
  • Anginal
  • Apo-Dipyridamole Fc
  • Apo-Dipyridamole Sc
  • Apricor
  • Cardioflux
  • Cardoxil
  • Chilcolan
  • Cleridium
  • Cleridium 150
  • Coribon
  • Coridil
  • Coronarine
  • Corosan
  • Coroxin
  • Curantyl
  • Dipyridan
  • Gulliostin
  • IV Persantine
  • Justpertin
  • Kurantil
  • Natyl
  • Novo-Dipiradol
  • Peridamol
  • Permiltin
  • Persantin
  • Persantine
  • Piroan
  • Prandiol
  • Prandiol 75
  • Protangix
  • RA 8
  • RA-8
  • Stenocardil
  • Stenocardiol
  • Stimolcardio
Brand name mixtures Not Available
Categories
  • Vasodilator Agents
  • Platelet Aggregation Inhibitors
  • Phosphodiesterase Inhibitors
CAS number 58-32-2
Weight Average: 504.6256
Monoisotopic: 504.317251808
Chemical Formula C24H40N8O4
InChI Key InChIKey=IZEKFCXSFNUWAM-UHFFFAOYSA-N
InChI
InChI=1S/C24H40N8O4/c33-15-11-31(12-16-34)23-26-20-19(21(27-23)29-7-3-1-4-8-29)25-24(32(13-17-35)14-18-36)28-22(20)30-9-5-2-6-10-30/h33-36H,1-18H2
Plain Text
IUPAC Name
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis(piperidin-1-yl)-[1,3]diazino[5,4-d]pyrimidin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol
SMILES
OCCN(CCO)C1=NC2=C(N=C(N=C2N2CCCCC2)N(CCO)CCO)C(=N1)N1CCCCC1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Pyrimidines and Derivatives
  • Piperidines
Substructures
  • Hydroxy Compounds
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Pyrimidines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Cyanamides
  • Piperidines
Pharmacology
Indication For as an adjunct to coumarin anticoagulants in the prevention of postoperative thromboembolic complications of cardiac valve replacement and also used in prevention of angina.
Pharmacodynamics Dipyridamole, a non-nitrate coronary vasodilator that also inhibits platelet aggregation, is combined with other anticoagulant drugs, such as warfarin, to prevent thrombosis in patients with valvular or vascular disorders. Dipyridamole is also used in myocardial perfusion imaging, as an antiplatelet agent, and in combination with aspirin for stroke prophylaxis.
Mechanism of action Dipyridamole likely inhibits both adenosine deaminase and phosphodiesterase, preventing the degradation of cAMP, an inhibitor of platelet function. This elevation in cAMP blocks the release of arachidonic acid from membrane phospholipids and reduces thromboxane A2 activity. Dipyridamole also directly stimulates the release of prostacyclin, which induces adenylate cyclase activity, thereby raising the intraplatelet concentration of cAMP and further inhibiting platelet aggregation.
Absorption 70%
Volume of distribution
  • 1 to 2.5 L/kg
Protein binding 99%
Metabolism

hepatic
Route of elimination Dipyridamole is metabolized in the liver to the glucuronic acid conjugate and excreted with the bile.
Half life 40 minutes
Clearance
  • 2.3-3.5 mL/min/kg
Toxicity Hypotension, if it occurs, is likely to be of short duration, but a vasopressor drug may be used if necessary. The oral LD50 in rats is greater than 6,000 mg/kg while in the dogs, the oral LD50 is approximately 400 mg/kg. LD50=8.4g/kg (orally in rat)
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00264 Dipyridamole (Antiplatelet) Pathway SMP00264
Pharmacoeconomics
Manufacturers
  • App pharmaceuticals llc
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Claris lifesciences ltd
  • Hospira inc
  • Teva parenteral medicines inc
  • Boehringer ingelheim pharmaceuticals inc
  • Actavis totowa llc
  • Barr laboratories inc
  • Glenmark generics inc usa
  • Impax laboratories inc
  • Lannett holdings inc
  • Murty pharmaceuticals inc
  • Purepac pharmaceutical co
  • Sandoz inc
  • Watson laboratories inc
  • Zydus pharmaceuticals usa inc
  • Boehringer Ingelheim Pharmaceuticals, Inc
Packagers
Dosage forms
Form Route Strength
Liquid Intravenous
Solution Intravenous
Tablet Oral
Prices
Unit description Cost Unit
Dipyridamole powder 5.34 USD g
Aggrenox capsule sa 3.25 USD capsule
Aggrenox 25-200 mg 12 Hour Capsule 3.0 USD capsule
Dipyridamole 5 mg/ml ampul 1.5 USD ml
Persantine 75 mg tablet 1.46 USD tablet
Dipyridamole 5 mg/ml vial 1.32 USD ml
Dipyridamole 75 mg tablet 1.28 USD tablet
Persantine 50 mg tablet 1.09 USD tablet
Dipyridamole 50 mg tablet 0.96 USD tablet
Persantine 25 mg tablet 0.89 USD tablet
Dipyridamole 25 mg tablet 0.58 USD tablet
Apo-Dipyridamole (Fc) 75 mg Tablet 0.46 USD tablet
Apo-Dipyridamole (Fc) 50 mg Tablet 0.31 USD tablet
Apo-Dipyridamole (Fc) 25 mg Tablet 0.28 USD tablet
Patents
Country Patent Number Approved Expires
United States 6015577 1997-01-18 2017-01-18
Properties
State solid
Melting point 163oC
Experimental Properties
Property Value Source
water solubility Slightly PhysProp
logP 1.5 PhysProp
Predicted Properties
Property Value Source
water solubility 9.22e-01 g/l ALOGPS
logP 1.52 ALOGPS
logP 1.81 ChemAxon Molconvert
logS -2.74 ALOGPS
pKa 15.40 ChemAxon Molconvert
hydrogen acceptor count 12 ChemAxon Molconvert
hydrogen donor count 4 ChemAxon Molconvert
polar surface area 145.44 ChemAxon Molconvert
rotatable bond count 12 ChemAxon Molconvert
refractivity 142.78 ChemAxon Molconvert
polarizability 56.94 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, Lowenthal A: European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996 Nov;143(1-2):1-13. Pubmed
External Links
Resource Link
KEGG Drug D00302 Link_out
PubChem Compound 3108 Link_out
PubChem Substance 46506292 Link_out
ChemSpider 2997 Link_out
BindingDB 23620 Link_out
ChEBI 4653 Link_out
ChEMBL 4653 Link_out
Therapeutic Targets Database DNC001625 Link_out
PharmGKB PA449367 Link_out
Drug Product Database 2244475 Link_out
RxList http://www.rxlist.com/cgi/generic2/dipyrid.htm Link_out
Drugs.com http://www.drugs.com/cdi/dipyridamole.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Dipyridamole Link_out
ATC Codes
  • B01AC07
  • C01DX20
AHFS Codes
  • 24:12.92
PDB Entries Not Available
FDA label show (48.7 KB)
MSDS show (73.3 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Coffee and tea can decrease the effect of dipyridamole.
  • Take with food to reduce irritation.
Targets

1. cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A

Pharmacological action: yes
Actions: inhibitor

Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This enzyme can hydrolyze both cAMP and cGMP, having a higher affinity for cAMP

Organism class: human
UniProt ID: Q9Y233 Link_out
Gene: PDE10A 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. Fujishige K, Kotera J, Michibata H, Yuasa K, Takebayashi S, Okumura K, Omori K: Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A). J Biol Chem. 1999 Jun 25;274(26):18438-45. Pubmed

2. Adenosine deaminase

Pharmacological action: yes
Actions: inhibitor

Adenosine + H(2)O = inosine + NH(3)

Organism class: human
UniProt ID: P00813 Link_out
Gene: ADA 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

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. Kulkarni SK, Patil CS: Phosphodiesterase 5 enzyme and its inhibitors: update on pharmacological and therapeutical aspects. Methods Find Exp Clin Pharmacol. 2004 Dec;26(10):789-99. Pubmed
  2. Santini F, Casali G, Franchi G, Auriemma S, Lusini M, Barozzi L, Favaro A, Messina A, Mazzucco A: Hemodynamic effects of inhaled nitric oxide and phosphodiesterase inhibitor (dipyridamole) on secondary pulmonary hypertension following heart valve surgery in adults. Int J Cardiol. 2005 Aug 18;103(2):156-63. Pubmed
  3. Kruuse C, Lassen LH, Iversen HK, Oestergaard S, Olesen J: Dipyridamole may induce migraine in patients with migraine without aura. Cephalalgia. 2006 Aug;26(8):925-33. Pubmed
  4. Jackson EK, Ren J, Zacharia LC, Mi Z: Characterization of renal ecto-phosphodiesterase. J Pharmacol Exp Ther. 2007 May;321(2):810-5. Epub 2007 Feb 16. Pubmed
  5. 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
Transporters

1. Multidrug resistance-associated protein 4

Actions: inhibitor

May be an organic anion pump relevant to cellular detoxification

UniProt ID: O15439 Link_out
Gene: ABCC4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. van Aubel RA, Smeets PH, Peters JG, Bindels RJ, Russel FG: The MRP4/ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules: putative efflux pump for urinary cAMP and cGMP. J Am Soc Nephrol. 2002 Mar;13(3):595-603. Pubmed
  2. Reid G, Wielinga P, Zelcer N, De Haas M, Van Deemter L, Wijnholds J, Balzarini J, Borst P: Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5. Mol Pharmacol. 2003 May;63(5):1094-103. Pubmed
  3. Rius M, Nies AT, Hummel-Eisenbeiss J, Jedlitschky G, Keppler D: Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Hepatology. 2003 Aug;38(2):374-84. Pubmed

2. Multidrug resistance-associated protein 5

Actions: inhibitor

Acts as a multispecific organic anion pump which can transport nucleotide analogs

UniProt ID: O15440 Link_out
Gene: ABCC5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Reid G, Wielinga P, Zelcer N, De Haas M, Van Deemter L, Wijnholds J, Balzarini J, Borst P: Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5. Mol Pharmacol. 2003 May;63(5):1094-103. Pubmed

3. Multidrug resistance protein 1

Actions: substrate, inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. Pubmed
  2. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:07

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.