生物活性

• 描述Platelet-derived growth factors (PDGFs) are composed of five kinds of ligand dimers, PDGF-AA, -BB, -AB, -CC, and -DD, which bind to three kinds of their receptor dimmers, PDGF receptor (PDGFR) αα, αβ, and ββ, with different affinities. The PDGFs transduce overlapping but not identical cellular signals, such as Src, JNK, Akt, and PLCγ, for regulating cellular properties, including proliferation and migration. Trapidil is a vasodilator and antiplatelet agent and also a platelet-derived growth factor antagonist. Trapidil at 100 µg/ml significantly inhibited the proliferation of U251MG cells, while there was no inhibitory effect on U105MG cells (which do not produce the PDGF-like molecule). Trapidil at 400 μM strongly inhibited osteoclastogenesis in mice by abrogating receptor activator of NF-kB ligand-induced calcium oscillation and Pim-1 expression required for NFATc1 (a master transcription factor for osteoclastogenesis) induction. It was also fund that trapidil treatment at 100 to 400 μg/ml significantly inhibited human mesangial cell proliferation, which might be related to the inhibition of PDGF-BB binding to its receptors and modulation of PDGFβ-receptor gene expression. Trapidil at 400 μg/ml inhibited the PDGF-stimulated MAP kinase activation by 35% at 10 minutes and by 32% at 6 hours but had no effect on MAP kinase protein expression levels.

• 动物研究
  剂量	Rabbit: 30 mg/kg[3] (s.c., BID) Rat: 4 mg/kg, 20 mg/kg[4] (i.p.), 30 mg/kg - 90 mg/kg[5] (i.p., lethal dose: 90 mg/kg); 100 mg/kg[6] (p.o.)
  给药途径	s.c., i.p., p.o.