Identification

Name
Trapidil
Accession Number
DB09283
Type
Small Molecule
Groups
Experimental
Description

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.

Structure
Thumb
Synonyms
Not Available
Categories
UNII
EYG5Y6355E
CAS number
15421-84-8
Weight
Average: 205.265
Monoisotopic: 205.132745503
Chemical Formula
C10H15N5
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

Pharmacology

Indication

Used in the treatment of chronic stable angina [8].

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
UPlatelet derived growth factor receptor beta
antagonist
Human
ACyclic nucleotide phosphodiesterase
inhibitor
Human
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].

Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbciximabTrapidil may increase the anticoagulant activities of Abciximab.
AcenocoumarolThe risk or severity of bleeding can be increased when Trapidil is combined with Acenocoumarol.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Trapidil is combined with Acetylsalicylic acid.
AloxiprinThe risk or severity of adverse effects can be increased when Trapidil is combined with Aloxiprin.
AlteplaseTrapidil may increase the anticoagulant activities of Alteplase.
Aminosalicylic AcidThe risk or severity of adverse effects can be increased when Trapidil is combined with Aminosalicylic Acid.
AnagrelideTrapidil may increase the anticoagulant activities of Anagrelide.
AncrodTrapidil may increase the anticoagulant activities of Ancrod.
AndrographolideAndrographolide may increase the antiplatelet activities of Trapidil.
AnistreplaseTrapidil may increase the anticoagulant activities of Anistreplase.
Food Interactions
Not Available

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. [PubMed:6894333]
  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. [PubMed:6265246]
  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. [PubMed:6264257]
  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. [PubMed:6086387]
  5. Catterall WA: Voltage-gated calcium channels. Cold Spring Harb Perspect Biol. 2011 Aug 1;3(8):a003947. doi: 10.1101/cshperspect.a003947. [PubMed:21746798]
  6. Hoshiya M, Awazu M: Trapidil inhibits platelet-derived growth factor-stimulated mitogen-activated protein kinase cascade. Hypertension. 1998 Feb;31(2):665-71. [PubMed:9461238]
  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. [PubMed:21484090]
  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. [PubMed:8904615]
External Links
PubChem Compound
5531
PubChem Substance
310265176
ChemSpider
5330
ChEBI
32254
ChEMBL
CHEMBL132767
Wikipedia
Trapidil
ATC Codes
C01DX11 — Trapidil
MSDS
Download (56.4 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
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
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0bt9-3910000000-b908334d1b56aa6fde4b

Taxonomy

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
Triazolopyrimidine / Dialkylarylamine / Aminopyrimidine / Pyrimidine / Heteroaromatic compound / 1,2,4-triazole / Triazole / Azole / Azacycle / Organic nitrogen compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

1. Platelet derived growth factor receptor beta
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
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. [PubMed:9461238]
Kind
Protein group
Organism
Human
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. [PubMed:6086387]

Drug created on October 29, 2015 10:07 / Updated on October 01, 2018 14:49