(Rac)-Modipafant(UK-74505)是一种口服的、选择性的、长效的不可逆血小板活化因子受体(PAFR)受体拮抗剂。(Rac)-Modipafant预防严重登革热感染。
(Rac)-Modipafant (UK-74505) is an orally active, selective, long-acting irreversible platelet activating factor receptor (PAFR) antagonist. (Rac)-Modipafant prevents dengue infection[1][2][3].
(Rac)-Modipafant (UK-74505) (10 mg/kg; p.o.; twice a day until day 10) prevents Severe Dengue Infection[3].(Rac)-Modipafant exhibits highly selective, time-dependent inhibition of PAF-induced aggregation of rabbit washed platelets (IC50=26.3 and 1.12 nM after 0.25 and 60 min preincubation, respectively)[4].(Rac)-Modipafant (5-20 mg/kg; p.o.) dose-dependently inhibits the Zymosan -induced articular hyperalgesia[5]. Animal Model: 8- to 10-week-old BALB/c mice (DEN-2 strain infected)[3]
[1]. O'Connor BJ, et al. Inhibitory effect of UK,74505, a potent and specific oral platelet activating factor (PAF) receptor antagonist, on airway and systemic responses to inhaled PAF in humans. Am J Respir Crit Care Med. 1994;150(1):35-40. [2]. Alabaster VA, et al. UK-74,505, a novel and selective PAF antagonist, exhibits potent and long lasting activity in vivo. Agents Actions Suppl. 1991;34:221-227. [3]. Parry MJ, Alabaster VA, et al. Pharmacological profile of UK-74,505, a novel and selective PAF antagonist with potent and prolonged oral activity. J Lipid Mediat Cell Signal. 1994;10(3):251-268. [4]. Souza DG, et al. Essential role of platelet-activating factor receptor in the pathogenesis of Dengue virus infection. Proc Natl Acad Sci U S A. 2009;106(33):14138-14143. [5]. Guerrero AT, et al. The role of PAF/PAFR signaling in zymosan-induced articular inflammatory hyperalgesia [published correction appears in Naunyn Schmiedebergs Arch Pharmacol. 2013 Apr;386(4):351. Zaperlon, Ana C [corrected to Zarpelon, Ana C]]. Naunyn Schmiedebergs Arch Pharmacol. 2013;386(1):51-59.
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