Trapidil
Identification
- Generic Name
- Trapidil
- DrugBank Accession Number
- DB09283
- Background
Trapidil, a platelet-derived growth factor antagonist, was originally developed as a vasodilator and anti-platelet agent and has been used to treat patients with ischemic coronary heart, liver, and kidney disease.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
- Weight
- Average: 205.265
Monoisotopic: 205.132745503 - Chemical Formula
- C10H15N5
- Synonyms
- Trapidil
Pharmacology
- Indication
Used in the treatment of chronic stable angina 8.
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.- 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
Trapidil exerts vasodilatory and antiplatelet effects 1. It also inhibits the activity of platelet derived growth factor (PDGF) 3.
- Mechanism of action
Trapidil is thought to inhibit cyclic adenosine monophosphate (cAMP) phosphodiesterase enzymes 4. The resultant increase in cAMP potentiates the inhibition of platelets by adenosine 7. The reduction in platelet activation is likely responsible for the decrease in thromboxane A2 generation seen with trapidil 1. The increase in cAMP is also likely responsible for the vasdilatory action of trapidil. The increase in protein kinase A activity due to increased cAMP activated L-type calcium channels in the heart leading to increased depolarization and a positive inotropic effect 2,5. Lastly, PKA inactivates Raf-1, an activator of mitogen activated protein kinase (MAPK), which leads to a reduction in MAPK activation. This reduction in MAPK prevents mitogenesis due to PDGF binding to PDGF receptors 6.
Target Actions Organism ACyclic nucleotide phosphodiesterase inhibitorHumans UPlatelet-derived growth factor receptor beta antagonistHumans - Absorption
Trapidil has a Tmax of 1 h 8.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
The half life of elimination is 1.31 h for a single dose and 1.14 h for steady state dosing 8.
- Clearance
The apparent clearance is 179 mL/min for a single dose and 273 mL/min for steady state dosing 8.
- 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
Not Available
- Pathways
- Not Available
- 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 softwareAbciximab The risk or severity of bleeding can be increased when Trapidil is combined with Abciximab. Abrocitinib The risk or severity of bleeding and thrombocytopenia can be increased when Trapidil is combined with Abrocitinib. Aceclofenac The risk or severity of bleeding can be increased when Aceclofenac is combined with Trapidil. Acemetacin The risk or severity of bleeding can be increased when Acemetacin is combined with Trapidil. Acenocoumarol The risk or severity of bleeding can be increased when Trapidil is combined with Acenocoumarol. - Food Interactions
- Not Available
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.
Categories
- ATC Codes
- C01DX11 — Trapidil
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as triazolopyrimidines. These are polycyclic aromatic compounds containing triazole ring fused to a pyrimidine ring. Triazole is a five-membered ring consisting of two carbon atoms and three nitrogen atoms. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Triazolopyrimidines
- Sub Class
- Not Available
- Direct Parent
- Triazolopyrimidines
- Alternative Parents
- Dialkylarylamines / Aminopyrimidines and derivatives / Triazoles / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- 1,2,4-triazole / Aminopyrimidine / Aromatic heteropolycyclic compound / Azacycle / Azole / Dialkylarylamine / Heteroaromatic compound / Hydrocarbon derivative / Organic nitrogen compound / Organonitrogen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- EYG5Y6355E
- CAS number
- 15421-84-8
- InChI Key
- GSNOZLZNQMLSKJ-UHFFFAOYSA-N
- InChI
- InChI=1S/C10H15N5/c1-4-14(5-2)9-6-8(3)13-10-11-7-12-15(9)10/h6-7H,4-5H2,1-3H3
- IUPAC Name
- N,N-diethyl-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
- SMILES
- CCN(CC)C1=CC(C)=NC2=NC=NN12
References
- General References
- Ohnishi H, Kosuzume H, Hayashi Y, Yamaguchi K, Suzuki Y, Itoh R: Effects of trapidil on thromboxane A2-induced aggregation of platelets, ischemic changes in heart and biosynthesis of thromboxane A2. Prostaglandins Med. 1981 Mar;6(3):269-81. [Article]
- Azuma J, Sawamura A, Harada H, Tanimoto T, Morita Y, Sperelakis N, Yamamura Y: Trapidil stimulation of slow Ca2+ current in cardiac muscle. Eur J Pharmacol. 1981 Jun 19;72(2-3):199-208. [Article]
- Ohnishi H, Yamaguchi K, Shimada S, Suzuki Y, Kumagai A: A new approach to the treatment of atherosclerosis and trapidil as an antagonist to platelet-derived growth factor. Life Sci. 1981 Apr 6;28(14):1641-6. [Article]
- Mazurov AV, Menshikov MYu, Leytin VL, Tkachuk VA, Repin VS: Decrease of platelet aggregation and spreading via inhibition of the cAMP phosphodiesterase by trapidil. FEBS Lett. 1984 Jul 9;172(2):167-71. [Article]
- Catterall WA: Voltage-gated calcium channels. Cold Spring Harb Perspect Biol. 2011 Aug 1;3(8):a003947. doi: 10.1101/cshperspect.a003947. [Article]
- Hoshiya M, Awazu M: Trapidil inhibits platelet-derived growth factor-stimulated mitogen-activated protein kinase cascade. Hypertension. 1998 Feb;31(2):665-71. [Article]
- Johnston-Cox HA, Ravid K: Adenosine and blood platelets. Purinergic Signal. 2011 Sep;7(3):357-65. doi: 10.1007/s11302-011-9220-4. Epub 2011 Feb 8. [Article]
- Harder S, Thurmann PA, Hellstern A, Benjaminov A: Pharmacokinetics of trapidil, an antagonist of platelet derived growth factor, in healthy subjects and in patients with liver cirrhosis. Br J Clin Pharmacol. 1996 Oct;42(4):443-9. [Article]
- External Links
- PubChem Compound
- 5531
- PubChem Substance
- 310265176
- ChemSpider
- 5330
- BindingDB
- 50240032
- 10735
- ChEBI
- 32254
- ChEMBL
- CHEMBL132767
- ZINC
- ZINC000000002202
- PDBe Ligand
- K1S
- Wikipedia
- Trapidil
- PDB Entries
- 5qjq / 5rk4 / 5smf
- MSDS
- Download (56.4 KB)
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Pill Tablet Injection, solution Intravenous Tablet, coated - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility 41 mg/mL MSDS - Predicted Properties
Property Value Source Water Solubility 1.93 mg/mL ALOGPS logP 1.85 ALOGPS logP 1.25 Chemaxon logS -2 ALOGPS pKa (Strongest Basic) 1.02 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 46.32 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 71.38 m3·mol-1 Chemaxon Polarizability 22.55 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 153.0871564 predictedDarkChem Lite v0.1.0 [M-H]- 142.40706 predictedDeepCCS 1.0 (2019) [M+H]+ 154.0167564 predictedDarkChem Lite v0.1.0 [M+H]+ 145.60454 predictedDeepCCS 1.0 (2019) [M+Na]+ 153.7114564 predictedDarkChem Lite v0.1.0 [M+Na]+ 154.224 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Metal ion binding
- Specific Function
- Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a higher affinity for cG...
Components:
References
- Mazurov AV, Menshikov MYu, Leytin VL, Tkachuk VA, Repin VS: Decrease of platelet aggregation and spreading via inhibition of the cAMP phosphodiesterase by trapidil. FEBS Lett. 1984 Jul 9;172(2):167-71. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Vascular endothelial growth factor binding
- Specific Function
- Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...
- Gene Name
- PDGFRB
- Uniprot ID
- P09619
- Uniprot Name
- Platelet-derived growth factor receptor beta
- Molecular Weight
- 123966.895 Da
References
- Hoshiya M, Awazu M: Trapidil inhibits platelet-derived growth factor-stimulated mitogen-activated protein kinase cascade. Hypertension. 1998 Feb;31(2):665-71. [Article]
Drug created at October 29, 2015 16:07 / Updated at February 21, 2021 18:52