Dipyridamole
Explore a selection of our essential drug information below, or:
Identification
- Summary
Dipyridamole is a phosphodiesterase inhibitor used to prevent postoperative thromboembolic events.
- Brand Names
- Aggrenox, Persantine
- Generic Name
- Dipyridamole
- DrugBank Accession Number
- DB00975
- Background
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)
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 504.6256
Monoisotopic: 504.317251808 - Chemical Formula
- C24H40N8O4
- Synonyms
- Dipiridamol
- Dipyridamine
- Dipyridamole
- Dipyridamolum
- Dipyudamine
- Dypyridamol
- External IDs
- NSC-515776
- USAF GE-12
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.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Diagnostic agent Coronary artery disease •••••••••••• •••••••••• •••••••••• •••••••• Adjunct therapy in prevention of Postoperative thromboembolism •••••••••••• Prevention of Stroke •••••••••••• •••••••• •••••• ••••••• Used in combination to prevent Stroke Regimen in combination with: Acetylsalicylic acid (DB00945) •••••••••••• •••••••• •••••• ••••••• Used in combination to prevent Stroke Combination Product in combination with: Acetylsalicylic acid (DB00945) •••••••••••• - Associated Therapies
- Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- 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.
Target Actions Organism AcAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A inhibitorHumans AcGMP-specific 3',5'-cyclic phosphodiesterase inhibitorHumans A3',5'-cyclic-AMP phosphodiesterase 4A inhibitorHumans AAdenosine deaminase inhibitorHumans UCalcipressin-1 Not Available Humans UAlpha-1-acid glycoprotein 1 Not Available Humans - 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
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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)
- Pathways
Pathway Category Dipyridamole (Antiplatelet) Action Pathway Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbaloparatide The risk or severity of adverse effects can be increased when Dipyridamole is combined with Abaloparatide. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Dipyridamole. Abrocitinib The risk or severity of bleeding and thrombocytopenia can be increased when Dipyridamole is combined with Abrocitinib. Acebutolol Dipyridamole may increase the bradycardic activities of Acebutolol. Aceclofenac The risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Dipyridamole. - Food Interactions
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
- Avoid xanthines. Xanthines, found in coffee and tea, can reduce the effectiveness of this medication.
- Take with or without food. Taking dipyridamole extrended release capusels with a high-fat meal minimally reduces it's AUC and Cmax.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Images
- International/Other Brands
- Agilease (lsei) / Cardoxin (Rafa) / Cleridium 150 (Millot) / Curantyl (Arzneimittelwerk) / Persantin
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Dipyridamole Injection, solution 5 mg/1mL Intravenous Hospira, Inc. 2006-04-07 Not applicable US Dipyridamole Solution 5 mg/1mL Intravenous Anazao Health Corporation 2012-05-23 Not applicable US Dipyridamole Injection, solution 5 mg/1mL Intravenous Hospira, Inc. 2006-04-07 Not applicable US Dipyridamole 25 Tab 25mg Tablet 25 mg Oral Pro Doc Limitee 1983-12-31 2002-08-02 Canada Dipyridamole 50 Tab 50mg Tablet 50 mg Oral Pro Doc Limitee 1983-12-31 2002-08-02 Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-dipyridamole Tablet 100 mg Oral Apotex Corporation Not applicable Not applicable Canada Apo-dipyridamole Tablet 75 mg Oral Apotex Corporation 1990-12-31 Not applicable Canada Apo-dipyridamole Tablet 50 mg Oral Apotex Corporation 1990-12-31 Not applicable Canada Apo-dipyridamole Tablet 25 mg Oral Apotex Corporation 1990-12-31 Not applicable Canada Apo-dipyridamole-SC Tab 25mg Tablet 25 mg Oral Apotex Corporation 1982-12-31 Not applicable Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Aggrenox Dipyridamole (200 mg/1) + Acetylsalicylic acid (25 mg/1) Capsule Oral Rebel Distributors 1999-12-19 Not applicable US Aggrenox Dipyridamole (200 mg/1) + Acetylsalicylic acid (25 mg/1) Capsule, extended release Oral Boehringer Ingelheim Pharmaceuticals, Inc. 1999-12-19 Not applicable US AGGRENOX Dipyridamole (200 MG) + Acetylsalicylic acid (25 MG) Capsule Oral Boehringer Ingelheim 2014-07-08 2016-06-12 Italy Aggrenox Dipyridamole (200 mg/1) + Acetylsalicylic acid (25 mg/1) Capsule, extended release Oral Carilion Materials Management 1999-12-19 Not applicable US AGGRENOX Dipyridamole (200 MG) + Acetylsalicylic acid (25 MG) Capsule Oral Boehringer Ingelheim 2014-07-08 2021-05-07 Italy - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Dipyridamole Dipyridamole (5 mg/1mL) Solution Intravenous Anazao Health Corporation 2012-05-23 Not applicable US
Categories
- ATC Codes
- B01AC07 — Dipyridamole
- Drug Categories
- Anticoagulants
- Antiplatelet agents
- Blood and Blood Forming Organs
- BSEP/ABCB11 Substrates
- Cardiovascular Agents
- Decreased Platelet Aggregation
- Enzyme Inhibitors
- Hematologic Agents
- Hypotensive Agents
- Miscellaneous Vasodilatating Agents
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- Organic Anion Transporting Polypeptide 2B1 Inhibitors
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Phosphodiesterase 5 Inhibitors
- Phosphodiesterase Inhibitors
- Platelet Aggregation Inhibitors Excl. Heparin
- Pyrimidines
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dialkylarylamines. These are aliphatic aromatic amines in which the amino group is linked to two aliphatic chains and one aromatic group.
- Kingdom
- Organic compounds
- Super Class
- Organic nitrogen compounds
- Class
- Organonitrogen compounds
- Sub Class
- Amines
- Direct Parent
- Dialkylarylamines
- Alternative Parents
- Aminopyrimidines and derivatives / Piperidines / Imidolactams / Heteroaromatic compounds / Azacyclic compounds / Alkanolamines / Primary alcohols / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- Alcohol / Alkanolamine / Aminopyrimidine / Aromatic heteropolycyclic compound / Azacycle / Dialkylarylamine / Heteroaromatic compound / Hydrocarbon derivative / Imidolactam / Organic oxygen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- piperidines, tertiary amino compound, tetrol, pyrimidopyrimidine (CHEBI:4653)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 64ALC7F90C
- CAS number
- 58-32-2
- InChI Key
- 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
- 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
References
- Synthesis Reference
Minutza Leibovici, Itamar Kanari, Michael Fox, "Dipyridamole extended-release formulations and process for preparing same." U.S. Patent US20070184110, issued August 09, 2007.
US20070184110- General References
- 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. [Article]
- External Links
- Human Metabolome Database
- HMDB0015110
- KEGG Drug
- D00302
- PubChem Compound
- 3108
- PubChem Substance
- 46506292
- ChemSpider
- 2997
- BindingDB
- 23620
- 3521
- ChEBI
- 4653
- ChEMBL
- CHEMBL932
- ZINC
- ZINC000000643046
- Therapeutic Targets Database
- DNC001625
- PharmGKB
- PA449367
- PDBe Ligand
- H9F
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Dipyridamole
- PDB Entries
- 7dmc / 8i4a / 8t6u
- FDA label
- Download (48.7 KB)
- MSDS
- Download (73.3 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Atherosclerosis / Cardiovascular Disease (CVD) / Stenosis, Carotid / Stroke 1 somestatus stop reason just information to hide Not Available Completed Basic Science Hyperemia / Hypoxia 1 somestatus stop reason just information to hide Not Available Completed Prevention Cirrhosis of the Liver / Portal Hypertension / Splenectomy / Venous Thrombosis (Disorder) 1 somestatus stop reason just information to hide Not Available Completed Treatment Schizoaffective Disorders / Schizophrenia / Schizophreniform Disorders 1 somestatus stop reason just information to hide Not Available Completed Treatment Stroke / Transient Ischemic Attack 1 somestatus stop reason just information to hide
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
- Amerisource Health Services Corp.
- Apotex Inc.
- APP Pharmaceuticals
- Avkare Incorporated
- Barr Pharmaceuticals
- Baxter International Inc.
- Bedford Labs
- Ben Venue Laboratories Inc.
- Boehringer Ingelheim Ltd.
- Cadila Healthcare Ltd.
- Cardinal Health
- Direct Dispensing Inc.
- Dispensing Solutions
- General Injectables and Vaccines Inc.
- Glenmark Generics Ltd.
- Global Pharmaceuticals
- Group Health Cooperative
- H and H Laboratories
- Heartland Repack Services LLC
- Hospira Inc.
- Impax Laboratories Inc.
- Kaiser Foundation Hospital
- Lake Erie Medical and Surgical Supply
- Lannett Co. Inc.
- Major Pharmaceuticals
- Mallinckrodt Inc.
- Mead Johnson and Co.
- Murfreesboro Pharmaceutical Nursing Supply
- Murty Pharmaceuticals Inc.
- Novex Pharma
- PCA LLC
- PD-Rx Pharmaceuticals Inc.
- Pharmaceutical Utilization Management Program VA Inc.
- Physicians Total Care Inc.
- Prepak Systems Inc.
- Qualitest
- Rebel Distributors Corp.
- Resource Optimization and Innovation LLC
- Rising Pharmaceuticals
- Sandhills Packaging Inc.
- Sicor Pharmaceuticals
- Southwood Pharmaceuticals
- Spectrum Pharmaceuticals
- Teva Pharmaceutical Industries Ltd.
- UDL Laboratories
- Vangard Labs Inc.
- Zydus Pharmaceuticals
- Dosage Forms
Form Route Strength Capsule Oral Capsule Oral 25.000 MG Capsule, extended release Oral Tablet Oral 50 mg Capsule, delayed release Oral Tablet Oral Tablet, coated Oral 100 mg Injection Intravenous 5 mg/1mL Injection, solution Intravenous 5 mg/1mL Solution Intravenous 5 mg/1mL Tablet Oral 25 mg/1 Tablet Oral 50 mg/1 Tablet Oral 75 mg/1 Tablet, film coated Oral 25 mg/1 Tablet, film coated Oral 50 mg/1 Tablet, film coated Oral 75 mg/1 Liquid Intravenous 5 mg / mL Solution Parenteral 5 mg Tablet, delayed release Oral Tablet Oral 100 mg Pill Tablet, sugar coated Oral 25 mg Tablet, sugar coated Oral 75 mg Capsule 200 MG Injection, solution Intravenous 10 MG/2ML Pill 75 MG Solution Parenteral 10.000 mg Tablet Oral 75.000 mg Tablet, coated Oral Solution Intravenous 10 mg Solution Intravenous; Parenteral 10 mg Tablet, delayed release Oral 75 mg Injection Intramuscular; Intravenous 10 mg/2ml Solution Intravenous 5 mg / mL Tablet, coated Oral 25 mg/1 Tablet, coated Oral 50 mg/1 Tablet, coated Oral 75 mg/1 Tablet Oral 25 mg Tablet Oral 75 mg Tablet, film coated Oral 75 mg Tablet, coated Oral 75 mg Tablet, coated Oral 25 mg - Prices
Unit description Cost Unit Dipyridamole powder 5.34USD g Aggrenox capsule sa 3.25USD capsule Aggrenox 25-200 mg 12 Hour Capsule 3.0USD capsule Dipyridamole 5 mg/ml ampul 1.5USD ml Persantine 75 mg tablet 1.46USD tablet Dipyridamole 5 mg/ml vial 1.32USD ml Dipyridamole 75 mg tablet 1.28USD tablet Persantine 50 mg tablet 1.09USD tablet Dipyridamole 50 mg tablet 0.96USD tablet Persantine 25 mg tablet 0.89USD tablet Dipyridamole 25 mg tablet 0.58USD tablet Apo-Dipyridamole (Fc) 75 mg Tablet 0.46USD tablet Apo-Dipyridamole (Fc) 50 mg Tablet 0.31USD tablet Apo-Dipyridamole (Fc) 25 mg Tablet 0.28USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6015577 No 2000-01-18 2017-01-18 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 163 °C PhysProp water solubility Slightly Not Available logP 1.5 Not Available - Predicted Properties
Property Value Source Water Solubility 0.922 mg/mL ALOGPS logP 1.52 ALOGPS logP 1.81 Chemaxon logS -2.7 ALOGPS pKa (Strongest Acidic) 14.97 Chemaxon pKa (Strongest Basic) 3.54 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 12 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 145.44 Å2 Chemaxon Rotatable Bond Count 12 Chemaxon Refractivity 142.78 m3·mol-1 Chemaxon Polarizability 56.93 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9917 Blood Brain Barrier - 0.6246 Caco-2 permeable - 0.7261 P-glycoprotein substrate Substrate 0.7696 P-glycoprotein inhibitor I Non-inhibitor 0.5321 P-glycoprotein inhibitor II Non-inhibitor 0.8383 Renal organic cation transporter Non-inhibitor 0.615 CYP450 2C9 substrate Non-substrate 0.8345 CYP450 2D6 substrate Non-substrate 0.6825 CYP450 3A4 substrate Non-substrate 0.6849 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Inhibitor 0.8045 CYP450 2D6 inhibitor Inhibitor 0.7201 CYP450 2C19 inhibitor Non-inhibitor 0.957 CYP450 3A4 inhibitor Inhibitor 0.6789 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7806 Ames test Non AMES toxic 0.7009 Carcinogenicity Non-carcinogens 0.8884 Biodegradation Not ready biodegradable 0.988 Rat acute toxicity 2.1167 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.5271 hERG inhibition (predictor II) Non-inhibitor 0.633
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 236.8521267 predictedDarkChem Lite v0.1.0 [M-H]- 236.6562267 predictedDarkChem Lite v0.1.0 [M-H]- 219.1389 predictedDeepCCS 1.0 (2019) [M+H]+ 235.7354267 predictedDarkChem Lite v0.1.0 [M+H]+ 235.8137267 predictedDarkChem Lite v0.1.0 [M+H]+ 221.4969 predictedDeepCCS 1.0 (2019) [M+Na]+ 235.6288267 predictedDarkChem Lite v0.1.0 [M+Na]+ 235.5341267 predictedDarkChem Lite v0.1.0 [M+Na]+ 227.79008 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides (PubMed:10373451, PubMed:10393245, PubMed:16330539, PubMed:17389385, PubMed:27058447). Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate (PubMed:10373451, PubMed:10393245, PubMed:17389385, PubMed:27058447). May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition (PubMed:27058447)
- Specific Function
- 3',5'-cyclic-AMP phosphodiesterase activity
- Gene Name
- PDE10A
- Uniprot ID
- Q9Y233
- Uniprot Name
- cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
- Molecular Weight
- 114945.16 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- 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 (PubMed:15489334, PubMed:9714779). Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334)
- Specific Function
- 3',5'-cyclic-AMP phosphodiesterase activity
- Gene Name
- PDE5A
- Uniprot ID
- O76074
- Uniprot Name
- cGMP-specific 3',5'-cyclic phosphodiesterase
- Molecular Weight
- 99984.14 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes
- Specific Function
- 3',5'-cyclic-AMP phosphodiesterase activity
- Gene Name
- PDE4A
- Uniprot ID
- P27815
- Uniprot Name
- 3',5'-cyclic-AMP phosphodiesterase 4A
- Molecular Weight
- 98142.155 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine (PubMed:16670267, PubMed:23193172, PubMed:26166670, PubMed:8452534, PubMed:9361033). Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4 (PubMed:20959412). Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion (PubMed:11772392). Enhances dendritic cell immunogenicity by affecting dendritic cell costimulatory molecule expression and cytokines and chemokines secretion (By similarity). Enhances CD4+ T-cell differentiation and proliferation (PubMed:20959412). Acts as a positive modulator of adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand affinity via conformational change (PubMed:23193172). Stimulates plasminogen activation (PubMed:15016824). Plays a role in male fertility (PubMed:21919946, PubMed:26166670). Plays a protective role in early postimplantation embryonic development (By similarity). Also responsible for the deamination of cordycepin (3'-deoxyadenosine), a fungal natural product that shows antitumor, antibacterial, antifungal, antivirus, and immune regulation properties (PubMed:26038697)
- Specific Function
- 2'-deoxyadenosine deaminase activity
- Gene Name
- ADA
- Uniprot ID
- P00813
- Uniprot Name
- Adenosine deaminase
- Molecular Weight
- 40764.13 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Inhibits calcineurin-dependent transcriptional responses by binding to the catalytic domain of calcineurin A (PubMed:12809556). Could play a role during central nervous system development (By similarity)
- Specific Function
- calcium-dependent protein serine/threonine phosphatase regulator activity
- Gene Name
- RCAN1
- Uniprot ID
- P53805
- Uniprot Name
- Calcipressin-1
- Molecular Weight
- 28078.425 Da
References
- Mulero MC, Aubareda A, Orzaez M, Messeguer J, Serrano-Candelas E, Martinez-Hoyer S, Messeguer A, Perez-Paya E, Perez-Riba M: Inhibiting the calcineurin-NFAT (nuclear factor of activated T cells) signaling pathway with a regulator of calcineurin-derived peptide without affecting general calcineurin phosphatase activity. J Biol Chem. 2009 Apr 3;284(14):9394-401. doi: 10.1074/jbc.M805889200. Epub 2009 Feb 3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
- Specific Function
- Not Available
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23539.43 Da
References
- Herve F, Duche JC, d'Athis P, Marche C, Barre J, Tillement JP: Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Pharmacogenetics. 1996 Oct;6(5):403-15. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins (PubMed:11856762, PubMed:12523936, PubMed:12835412, PubMed:12883481, PubMed:15364914, PubMed:15454390, PubMed:16282361, PubMed:17959747, PubMed:18300232, PubMed:26721430). Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 (PubMed:17959747). Mediates the cotransport of bile acids with reduced glutathione (GSH) (PubMed:12523936, PubMed:12883481, PubMed:16282361). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules (PubMed:11856762, PubMed:12105214, PubMed:15454390, PubMed:17344354, PubMed:18300232). Confers resistance to anticancer agents such as methotrexate (PubMed:11106685)
- Specific Function
- 15-hydroxyprostaglandin dehydrogenase (NAD+) activity
- Gene Name
- ABCC4
- Uniprot ID
- O15439
- Uniprot Name
- ATP-binding cassette sub-family C member 4
- Molecular Weight
- 149525.33 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of endogenous metabolites such as cAMP and cGMP, folic acid and N-lactoyl-amino acids (in vitro) (PubMed:10893247, PubMed:12637526, PubMed:12695538, PubMed:15899835, PubMed:17229149, PubMed:25964343). Acts also as a general glutamate conjugate and analog transporter that can limit the brain levels of endogenous metabolites, drugs, and toxins (PubMed:26515061). Confers resistance to the antiviral agent PMEA (PubMed:12695538). Able to transport several anticancer drugs including methotrexate, and nucleotide analogs in vitro, however it does with low affinity, thus the exact role of ABCC5 in mediating resistance still needs to be elucidated (PubMed:10840050, PubMed:12435799, PubMed:12695538, PubMed:15899835). Acts as a heme transporter required for the translocation of cytosolic heme to the secretory pathway (PubMed:24836561). May play a role in energy metabolism by regulating the glucagon-like peptide 1 (GLP-1) secretion from enteroendocrine cells (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCC5
- Uniprot ID
- O15440
- Uniprot Name
- ATP-binding cassette sub-family C member 5
- Molecular Weight
- 160658.8 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10779507, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) (PubMed:10779507, PubMed:11159893, PubMed:12568656, PubMed:15159445, PubMed:17412826, PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Involved in the clearance of bile acids and organic anions from the liver (PubMed:22232210). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:15159445). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
References
- Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent transport of steroid sulfate conjugates and other specific organic anions (PubMed:10873595, PubMed:11159893, PubMed:11932330, PubMed:12724351, PubMed:14610227, PubMed:16908597, PubMed:18501590, PubMed:20507927, PubMed:22201122, PubMed:23531488, PubMed:25132355, PubMed:26383540, PubMed:27576593, PubMed:28408210, PubMed:29871943, PubMed:34628357). Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) (PubMed:11932330, PubMed:12409283). Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver (PubMed:11159893). Mediates the intestinal uptake of sulfated steroids (PubMed:12724351, PubMed:28408210). Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain (PubMed:16908597, PubMed:25132355). Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC (PubMed:35714613). Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition (PubMed:26383540). Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, PubMed:29871943, Ref.25). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:14610227, PubMed:19129463, PubMed:22201122). The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound (PubMed:19129463, PubMed:20507927, PubMed:26277985). Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions (PubMed:19129463). Cytoplasmic glutamate may also act as counteranion in the placenta (PubMed:26277985). An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) (PubMed:20507927)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO2B1
- Uniprot ID
- O94956
- Uniprot Name
- Solute carrier organic anion transporter family member 2B1
- Molecular Weight
- 76697.93 Da
References
- Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269)
- Specific Function
- ABC-type bile acid transporter activity
- Gene Name
- ABCB11
- Uniprot ID
- O95342
- Uniprot Name
- Bile salt export pump
- Molecular Weight
- 146405.83 Da
References
- Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [Article]
Drug created at June 13, 2005 13:24 / Updated at November 03, 2024 19:35