Identification

Name
Trapidil
Accession Number
DB09283
Type
Small Molecule
Groups
Approved
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].

Structured Indications
Not Available
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
DrugInteractionDrug group
AbciximabTrapidil may increase the anticoagulant activities of Abciximab.Approved
AcenocoumarolTrapidil may increase the anticoagulant activities of Acenocoumarol.Approved, Investigational
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Trapidil is combined with Acetylsalicylic acid.Approved, Vet Approved
AloxiprinThe risk or severity of adverse effects can be increased when Trapidil is combined with Aloxiprin.Experimental
AlprostadilAlprostadil may increase the antiplatelet activities of Trapidil.Approved, Investigational
AlteplaseTrapidil may increase the anticoagulant activities of Alteplase.Approved
Aminosalicylic AcidThe risk or severity of adverse effects can be increased when Trapidil is combined with Aminosalicylic Acid.Approved
AnagrelideTrapidil may increase the anticoagulant activities of Anagrelide.Approved
AncrodTrapidil may increase the anticoagulant activities of Ancrod.Approved, Investigational
AndrographolideAndrographolide may increase the antiplatelet activities of Trapidil.Investigational
AnistreplaseTrapidil may increase the anticoagulant activities of Anistreplase.Approved
Antithrombin III humanTrapidil may increase the anticoagulant activities of Antithrombin III human.Approved
ApixabanThe risk or severity of adverse effects can be increased when Trapidil is combined with Apixaban.Approved
ArdeparinTrapidil may increase the anticoagulant activities of Ardeparin.Approved, Investigational, Withdrawn
ArgatrobanTrapidil may increase the anticoagulant activities of Argatroban.Approved, Investigational
AstaxanthinTrapidil may increase the anticoagulant activities of Astaxanthin.Investigational
AzelastineAzelastine may increase the antiplatelet activities of Trapidil.Approved
BalsalazideThe risk or severity of adverse effects can be increased when Trapidil is combined with Balsalazide.Approved, Investigational
BatroxobinTrapidil may increase the anticoagulant activities of Batroxobin.Experimental
BecaplerminTrapidil may increase the anticoagulant activities of Becaplermin.Approved, Investigational
BemiparinTrapidil may increase the anticoagulant activities of Bemiparin.Approved, Investigational
BeraprostTrapidil may increase the anticoagulant activities of Beraprost.Investigational
BivalirudinTrapidil may increase the anticoagulant activities of Bivalirudin.Approved, Investigational
BrinaseTrapidil may increase the anticoagulant activities of Brinase.Experimental
BuflomedilTrapidil may increase the antiplatelet activities of Buflomedil.Experimental
ButylphthalideTrapidil may increase the antiplatelet activities of Butylphthalide.Investigational
CangrelorTrapidil may increase the anticoagulant activities of Cangrelor.Approved
CaplacizumabTrapidil may increase the anticoagulant activities of Caplacizumab.Investigational
Carbaspirin calciumThe risk or severity of adverse effects can be increased when Trapidil is combined with Carbaspirin calcium.Experimental, Investigational
CertoparinTrapidil may increase the anticoagulant activities of Certoparin.Approved, Investigational
CilostazolTrapidil may increase the anticoagulant activities of Cilostazol.Approved, Investigational
Citric AcidTrapidil may increase the anticoagulant activities of Citric Acid.Approved, Nutraceutical, Vet Approved
ClopidogrelTrapidil may increase the anticoagulant activities of Clopidogrel.Approved
CloricromenTrapidil may increase the anticoagulant activities of Cloricromen.Experimental
ClorindioneTrapidil may increase the anticoagulant activities of Clorindione.Experimental
Collagenase clostridium histolyticumThe risk or severity of adverse effects can be increased when Trapidil is combined with Collagenase clostridium histolyticum.Approved, Investigational
Dabigatran etexilateTrapidil may increase the anticoagulant activities of Dabigatran etexilate.Approved
DalteparinTrapidil may increase the anticoagulant activities of Dalteparin.Approved
DanaparoidTrapidil may increase the anticoagulant activities of Danaparoid.Approved, Withdrawn
DarexabanTrapidil may increase the anticoagulant activities of Darexaban.Investigational
DasatinibDasatinib may increase the anticoagulant activities of Trapidil.Approved, Investigational
DefibrotideTrapidil may increase the anticoagulant activities of Defibrotide.Approved, Investigational
Deoxycholic AcidThe risk or severity of adverse effects can be increased when Trapidil is combined with Deoxycholic Acid.Approved
DersalazineThe risk or severity of adverse effects can be increased when Trapidil is combined with Dersalazine.Investigational
DesirudinTrapidil may increase the anticoagulant activities of Desirudin.Approved
DesmoteplaseTrapidil may increase the anticoagulant activities of Desmoteplase.Investigational
DextranTrapidil may increase the anticoagulant activities of Dextran.Approved, Investigational, Vet Approved
DicoumarolTrapidil may increase the anticoagulant activities of Dicoumarol.Approved
DiflunisalThe risk or severity of adverse effects can be increased when Trapidil is combined with Diflunisal.Approved, Investigational
DiphenadioneTrapidil may increase the anticoagulant activities of Diphenadione.Experimental
DipyridamoleTrapidil may increase the anticoagulant activities of Dipyridamole.Approved
DitazoleTrapidil may increase the anticoagulant activities of Ditazole.Approved, Withdrawn
Drotrecogin alfaTrapidil may increase the anticoagulant activities of Drotrecogin alfa.Approved, Investigational, Withdrawn
Edetic AcidTrapidil may increase the anticoagulant activities of Edetic Acid.Approved, Vet Approved
EdoxabanTrapidil may increase the anticoagulant activities of Edoxaban.Approved
EnoxaparinTrapidil may increase the anticoagulant activities of Enoxaparin.Approved
EpinastineEpinastine may increase the antiplatelet activities of Trapidil.Approved, Investigational
EplivanserinTrapidil may increase the anticoagulant activities of Eplivanserin.Investigational
eplivanserineTrapidil may increase the anticoagulant activities of eplivanserine.Investigational
EpoprostenolTrapidil may increase the anticoagulant activities of Epoprostenol.Approved
EptifibatideTrapidil may increase the anticoagulant activities of Eptifibatide.Approved, Investigational
Ethyl biscoumacetateTrapidil may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
Ferulic acidTrapidil may increase the anticoagulant activities of Ferulic acid.Experimental
FibrinolysinTrapidil may increase the anticoagulant activities of Fibrinolysin.Investigational
FluindioneTrapidil may increase the anticoagulant activities of Fluindione.Approved, Investigational
FondaparinuxTrapidil may increase the anticoagulant activities of Fondaparinux.Approved, Investigational
Fondaparinux sodiumTrapidil may increase the anticoagulant activities of Fondaparinux sodium.Approved, Investigational
GabexateTrapidil may increase the anticoagulant activities of Gabexate.Investigational
GlucosamineGlucosamine may increase the antiplatelet activities of Trapidil.Approved, Investigational
GuacetisalThe risk or severity of adverse effects can be increased when Trapidil is combined with Guacetisal.Experimental
Hemoglobin crosfumarilThe risk or severity of adverse effects can be increased when Trapidil is combined with Hemoglobin crosfumaril.Experimental
HeparinTrapidil may increase the anticoagulant activities of Heparin.Approved, Investigational
HigenamineTrapidil may increase the anticoagulant activities of Higenamine.Investigational
HydroxytyrosolTrapidil may increase the antiplatelet activities of Hydroxytyrosol.Investigational
Ibritumomab tiuxetanThe risk or severity of adverse effects can be increased when Trapidil is combined with Ibritumomab tiuxetan.Approved, Investigational
IbrutinibThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Trapidil.Approved
IbudilastIbudilast may increase the antiplatelet activities of Trapidil.Approved, Investigational
Icosapent ethylIcosapent ethyl may increase the antiplatelet activities of Trapidil.Approved, Investigational, Nutraceutical
IdraparinuxTrapidil may increase the anticoagulant activities of Idraparinux.Investigational
IfenprodilIfenprodil may increase the antiplatelet activities of Trapidil.Approved, Investigational, Withdrawn
IfetrobanTrapidil may increase the antiplatelet activities of Ifetroban.Investigational
IloprostTrapidil may increase the anticoagulant activities of Iloprost.Approved, Investigational
IndobufenTrapidil may increase the anticoagulant activities of Indobufen.Investigational
KetanserinTrapidil may increase the antiplatelet activities of Ketanserin.Investigational
LepirudinTrapidil may increase the anticoagulant activities of Lepirudin.Approved
LetaxabanTrapidil may increase the anticoagulant activities of Letaxaban.Investigational
LimaprostLimaprost may increase the antiplatelet activities of Trapidil.Approved, Investigational
LinsidomineTrapidil may increase the antiplatelet activities of Linsidomine.Experimental
MelagatranTrapidil may increase the anticoagulant activities of Melagatran.Experimental
MesalazineThe risk or severity of adverse effects can be increased when Trapidil is combined with Mesalazine.Approved
Methyl salicylateThe risk or severity of adverse effects can be increased when Trapidil is combined with Methyl salicylate.Approved, Vet Approved
MilrinoneMilrinone may increase the antiplatelet activities of Trapidil.Approved
NadroparinTrapidil may increase the anticoagulant activities of Nadroparin.Approved, Investigational
NafamostatTrapidil may increase the anticoagulant activities of Nafamostat.Approved, Investigational
NaftopidilTrapidil may increase the antiplatelet activities of Naftopidil.Investigational
NimesulideNimesulide may increase the antiplatelet activities of Trapidil.Approved, Investigational, Withdrawn
NitroaspirinThe risk or severity of adverse effects can be increased when Trapidil is combined with Nitroaspirin.Investigational
ObinutuzumabThe risk or severity of adverse effects can be increased when Trapidil is combined with Obinutuzumab.Approved, Investigational
OlsalazineThe risk or severity of adverse effects can be increased when Trapidil is combined with Olsalazine.Approved
Omega-3 fatty acidsOmega-3 fatty acids may increase the antiplatelet activities of Trapidil.Approved, Nutraceutical
OtamixabanTrapidil may increase the anticoagulant activities of Otamixaban.Investigational
OzagrelTrapidil may increase the anticoagulant activities of Ozagrel.Investigational
ParnaparinTrapidil may increase the anticoagulant activities of Parnaparin.Approved, Investigational
Pentaerythritol TetranitrateTrapidil may increase the anticoagulant activities of Pentaerythritol Tetranitrate.Approved
Pentosan PolysulfateThe risk or severity of adverse effects can be increased when Pentosan Polysulfate is combined with Trapidil.Approved
PentoxifyllinePentoxifylline may increase the antiplatelet activities of Trapidil.Approved, Investigational
PhenindioneTrapidil may increase the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonTrapidil may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
Phenyl aminosalicylateThe risk or severity of adverse effects can be increased when Trapidil is combined with Phenyl aminosalicylate.Approved
PicotamideTrapidil may increase the anticoagulant activities of Picotamide.Experimental
PrasugrelTrapidil may increase the anticoagulant activities of Prasugrel.Approved
Protein CTrapidil may increase the anticoagulant activities of Protein C.Approved
Protein S humanTrapidil may increase the anticoagulant activities of Protein S human.Approved
ProtocatechualdehydeTrapidil may increase the anticoagulant activities of Protocatechualdehyde.Approved
RamatrobanTrapidil may increase the antiplatelet activities of Ramatroban.Investigational
RelcovaptanTrapidil may increase the antiplatelet activities of Relcovaptan.Investigational
ResveratrolResveratrol may increase the antiplatelet activities of Trapidil.Approved, Experimental, Investigational
ReteplaseTrapidil may increase the anticoagulant activities of Reteplase.Approved, Investigational
ReviparinTrapidil may increase the anticoagulant activities of Reviparin.Approved, Investigational
RidogrelRidogrel may increase the antiplatelet activities of Trapidil.Approved
RivaroxabanTrapidil may increase the anticoagulant activities of Rivaroxaban.Approved
RosiglitazoneTrapidil may increase the anticoagulant activities of Rosiglitazone.Approved, Investigational
Salicylic acidThe risk or severity of adverse effects can be increased when Trapidil is combined with Salicylic acid.Approved, Investigational, Vet Approved
SarpogrelateTrapidil may increase the anticoagulant activities of Sarpogrelate.Investigational
SaruplaseTrapidil may increase the anticoagulant activities of Saruplase.Experimental
SelexipagTrapidil may increase the anticoagulant activities of Selexipag.Approved
SevofluraneSevoflurane may increase the antiplatelet activities of Trapidil.Approved, Vet Approved
SRT501SRT501 may increase the antiplatelet activities of Trapidil.Investigational
StreptokinaseTrapidil may increase the anticoagulant activities of Streptokinase.Approved, Investigational
SulodexideTrapidil may increase the anticoagulant activities of Sulodexide.Approved, Investigational
TenecteplaseTrapidil may increase the anticoagulant activities of Tenecteplase.Approved
TesmilifeneTesmilifene may increase the antiplatelet activities of Trapidil.Investigational
TicagrelorTrapidil may increase the anticoagulant activities of Ticagrelor.Approved
TiclopidineTrapidil may increase the anticoagulant activities of Ticlopidine.Approved
TinzaparinTrapidil may increase the anticoagulant activities of Tinzaparin.Approved
TioclomarolTrapidil may increase the anticoagulant activities of Tioclomarol.Experimental
TipranavirTipranavir may increase the antiplatelet activities of Trapidil.Approved, Investigational
TirofibanTrapidil may increase the anticoagulant activities of Tirofiban.Approved
TositumomabThe risk or severity of adverse effects can be increased when Trapidil is combined with Tositumomab.Approved, Investigational
TranilastTranilast may increase the antiplatelet activities of Trapidil.Approved, Investigational
TreprostinilTrapidil may increase the anticoagulant activities of Treprostinil.Approved, Investigational
TriflusalTrapidil may increase the anticoagulant activities of Triflusal.Approved, Investigational
Trolamine salicylateThe risk or severity of adverse effects can be increased when Trapidil is combined with Trolamine salicylate.Approved
TroxerutinTrapidil may increase the anticoagulant activities of Troxerutin.Investigational
UrokinaseTrapidil may increase the anticoagulant activities of Urokinase.Approved, Investigational, Withdrawn
Vitamin EVitamin E may increase the antiplatelet activities of Trapidil.Approved, Nutraceutical, Vet Approved
VorapaxarTrapidil may increase the anticoagulant activities of Vorapaxar.Approved
WarfarinTrapidil may increase the anticoagulant activities of Warfarin.Approved
XimelagatranTrapidil may increase the anticoagulant activities of Ximelagatran.Approved, Investigational, Withdrawn
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 May 01, 2018 23:58