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.

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Contraindications & Blackbox Warnings
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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.

TargetActionsOrganism
ACyclic nucleotide phosphodiesterase
inhibitor
Humans
UPlatelet-derived growth factor receptor beta
antagonist
Humans
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
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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.
DrugInteraction
AbciximabThe risk or severity of bleeding can be increased when Trapidil is combined with Abciximab.
AbrocitinibThe risk or severity of bleeding and thrombocytopenia can be increased when Trapidil is combined with Abrocitinib.
AceclofenacThe risk or severity of bleeding can be increased when Aceclofenac is combined with Trapidil.
AcemetacinThe risk or severity of bleeding can be increased when Acemetacin is combined with Trapidil.
AcenocoumarolThe risk or severity of bleeding can be increased when Trapidil is combined with Acenocoumarol.
Food Interactions
Not Available

Products

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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
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. Catterall WA: Voltage-gated calcium channels. Cold Spring Harb Perspect Biol. 2011 Aug 1;3(8):a003947. doi: 10.1101/cshperspect.a003947. [Article]
  6. Hoshiya M, Awazu M: Trapidil inhibits platelet-derived growth factor-stimulated mitogen-activated protein kinase cascade. Hypertension. 1998 Feb;31(2):665-71. [Article]
  7. 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]
  8. 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]
PubChem Compound
5531
PubChem Substance
310265176
ChemSpider
5330
BindingDB
50240032
RxNav
10735
ChEBI
32254
ChEMBL
CHEMBL132767
ZINC
ZINC000000002202
PDBe Ligand
K1S
Wikipedia
Trapidil
PDB Entries
5qjq / 5rk4 / 5smf
MSDS
Download (56.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Pill
Tablet
Injection, solutionIntravenous
Tablet, coated
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility41 mg/mLMSDS
Predicted Properties
PropertyValueSource
Water Solubility1.93 mg/mLALOGPS
logP1.85ALOGPS
logP1.25Chemaxon
logS-2ALOGPS
pKa (Strongest Basic)1.02Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area46.32 Å2Chemaxon
Rotatable Bond Count3Chemaxon
Refractivity71.38 m3·mol-1Chemaxon
Polarizability22.55 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0bt9-3910000000-b908334d1b56aa6fde4b
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0bt9-3910000000-b908334d1b56aa6fde4b
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0090000000-242a94645d56752e035d
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udi-0190000000-906fcdd41cf38768e22c
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a6r-0690000000-cc1f52e24735a13bfea1
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0ugl-3940000000-df4ee45a980d8e56de26
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-01pk-6900000000-ba3daf34f2d7029c6b99
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-01oy-7900000000-49b975416df90c34ac02
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-153.0871564
predicted
DarkChem Lite v0.1.0
[M-H]-142.40706
predicted
DeepCCS 1.0 (2019)
[M+H]+154.0167564
predicted
DarkChem Lite v0.1.0
[M+H]+145.60454
predicted
DeepCCS 1.0 (2019)
[M+Na]+153.7114564
predicted
DarkChem Lite v0.1.0
[M+Na]+154.224
predicted
DeepCCS 1.0 (2019)

Targets

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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
  1. 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
  1. 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