Trapidil is a vasodilator, an antiplatelet active molecule with specificity for platelet-derived growth factor.

Physicochemical Properties

Molecular Formula	C10H15N5
Molecular Weight	205.2596
Exact Mass	205.132
Elemental Analysis	C, 58.51; H, 7.37; N, 34.12
CAS #	15421-84-8
Related CAS #	15421-84-8
PubChem CID	5531
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Melting Point	98-99.4° (Pfeifer); 102-104° from heptane (Tenor)
Index of Refraction	1.626
LogP	1.45
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	3
Heavy Atom Count	15
Complexity	206
Defined Atom Stereocenter Count	0
SMILES	N(C([H])([H])C([H])([H])[H])(C([H])([H])C([H])([H])[H])C1=C([H])C(C([H])([H])[H])=NC2=NC([H])=NN12
InChi Key	GSNOZLZNQMLSKJ-UHFFFAOYSA-N
InChi Code	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
Chemical Name	N,N-diethyl-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Synonyms	AR 12008; AR-12008; AR12008
HS Tariff Code	2934.99.03.00
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	PDGF
ln Vitro	Trapidil breaks the autocrine loop by acting on PDGF and PDGF receptors.Significant antiproliferative activity has been demonstrated by tramadil[1]. The addition of 100–400 μg/ml trapidil significantly inhibited the growth of cells stimulated by various growth factors (FCS, PDGF-BB, bFGF, and EGF), with PDGF-BB stimulating Mesangial cell (MC) growth being most inhibited. The medication had a dose-dependent, presumably targeted effect. ADP, arachidonic acid, PAF, collagen, calcium ionophore, and other aggregating agents are all targets of the anti-platelet medication tramadil. It works by inhibiting thromboxane A2 biosynthesis, counteracting its effects at the receptor level, and promoting prostacyclin synthesis and release[2]. In co-cultures of bone marrow cells and osteoblasts, tratidil significantly reduced the formation of osteoclasts while having no effect on the expression of osteoprotegerin or receptor activator of NF-κB ligand (RANKL) in osteoblasts. Furthermore, trapidil inhibited the formation of osteoclasts from osteoclast precursors induced by RANKL. Without influencing the expression of c-Fos, which serves as a crucial upstream activator of NFATc1 during osteoclastogenesis, tramadil decreased the RANKL-induced expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), a master transcription factor for osteoclastogenesis. Moreover, it has been documented that rivatimil activates protein kinase A and inhibits phosphodiesterase, thromboxane A2, and CD40 signaling[3].
ln Vivo	Trapidil is an antiplatelet medication that specifically antagonizes platelet-derived growth factors and has antiproliferative effects following balloon angioplasty in rat and rabbit models[1]. In an animal model of interleukin-1-induced osteoclast formation and bone resorption, tramadil demonstrated a strong inhibitory effect. Following intraperitoneal injections of trapidil, no abnormal symptoms, including weight changes, diarrhea, elevated fever, and convulsions, were noted[3].
Cell Assay	The Trypan blue dye exclusion test and the LDH assay were used to assess cell viability. After being exposed to various mitogens and drugs, cells were seeded in serum-free medium. The cells' supernatants were obtained, centrifuged, and the concentration of LDH was measured. As a positive control, supernatants from cells that had been sonicated were employed. In order to completely rule out Trapidil having a cytotoxic effect on human MC, cells that had been cultured for four days both with and without the medication were challenged with new medium containing 10% FBS, and the rate of cell division was assessed.
Animal Protocol	ICR mice 5 or 20 mg/kg i.p.
ADME/Pharmacokinetics	Absorption, Distribution and Excretion Trapidil has a Tmax of 1 h. The apparent clearance is 179 mL/min for a single dose and 273 mL/min for steady state dosing. Biological Half-Life The half life of elimination is 1.31 h for a single dose and 1.14 h for steady state dosing.
References	[1]. Circulation . 1994 Dec;90(6):2710-5. [2]. Kidney Int . 1994 Oct;46(4):1002-9. [3]. Biochem Pharmacol . 2013 Sep 15;86(6):782-90.
Additional Infomation	Trapidil is a member of triazolopyrimidines. 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. A coronary vasodilator agent. Drug Indication Used in the treatment of chronic stable angina. Mechanism of Action Trapidil is thought to inhibit cyclic adenosine monophosphate (cAMP) phosphodiesterase enzymes. The resultant increase in cAMP potentiates the inhibition of platelets by adenosine. The reduction in platelet activation is likely responsible for the decrease in thromboxane A2 generation seen with trapidil. 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. 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. Pharmacodynamics Trapidil exerts vasodilatory and antiplatelet effects. It also inhibits the activity of platelet derived growth factor (PDGF).

Solubility Data

Solubility (In Vitro)	DMSO: ~41 mg/mL (~199.8 mM) Ethanol: ~41 mg/mL (~199.8 mM) Water: ~41 mg/mL (~199.8 mM)
Solubility (In Vivo)	Solubility in Formulation 1: 100 mg/mL (487.19 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.8719 mL	24.3593 mL	48.7187 mL
	5 mM	0.9744 mL	4.8719 mL	9.7437 mL
	10 mM	0.4872 mL	2.4359 mL	4.8719 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.