title: K-134, a phosphodiesterase 3 inhibitor, prevents brain damage by inhibiting thrombus formation in a rat cerebral infarction model.
abstract: BACKGROUND
  K-134 is a more potent antiplatelet drug with a selective inhibitory effect on phosphodiesterase 3 (PDE3) compared with its analogue, cilostazol.
  
  
  OBJECTIVE
  This study was performed to compare the ameliorating effects of K-134 and cilostazol on brain damage in an experimental photothrombotic cerebral infarction model.
  
  
  RESULTS
  We investigated the effects of oral preadministration of PDE3 inhibitors in a rat stroke model established by photothrombotic middle cerebral artery (MCA) occlusion. K-134 significantly prolonged MCA occlusion time at doses >10 mg/kg, and reduced cerebral infarct size at 30 mg/kg in the stroke model (n = 12, 87.5±5.6 vs. 126.8±7.5 mm(3), P<0.01), indicating its potent antithrombotic effect. On the other hand, the effects of cilostazol on MCA occlusion time and cerebral infarct size are relatively weak even at the high dosage of 300 mg/kg. Furthermore, K-134 blocked rat platelet aggregation more potently than cilostazol in vitro. Also in an arteriovenous shunt thrombosis model, K-134 showed an antithrombotic effect greater than cilostazol.
  
  
  CONCLUSIONS
  These findings suggest that K-134, which has strong antithrombotic activity, is a promising drug for prevention of cerebral infarction associated with platelet hyperaggregability.
authors.affiliation: Tokyo New Drug Research Laboratories, Kowa Company, Ltd., Tokyo, Japan. hiyosida@kowa.co.jp
authors.forename: Hideo
authors.initials: H
authors.lastname: Yoshida
authors.forename: Yuka
authors.initials: Y
authors.lastname: Ashikawa
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Itoh
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Akimune
authors.initials: A
authors.lastname: Asanuma
authors.forename: Sohei
authors.initials: S
authors.lastname: Tanabe
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Hidaka
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D058987:Phosphodiesterase 3 Inhibitors / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000517:prevention & control*; D014508:Urea / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D058987:Phosphodiesterase 3 Inhibitors; D011804:Quinolines; D014508:Urea; C116725:OPC 33509