(Rac)-Modipafant

Names

[ Name ]:
(Rac)-Modipafant

[Synonym ]:
ethyl 4-(2-chlorophenyl)-6-methyl-2-[4-(2-methylimidazo[4,5-c]pyridin-1-yl)phenyl]-5-(pyridin-2-ylcarbamoyl)-1,4-dihydropyridine-3-carboxylate

Biological Activity

[Description]:

(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].

[Related Catalog]:

Research Areas >> Infection

Signaling Pathways >> Others >> Others

Research Areas >> Inflammation/Immunology

[In Vivo]

(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] Dosage: 10 mg/kg Administration: P.o.; twice a day (started on days 0, 3, 5, or 7) until day 10 Result: Decreased by approximately 50% the lethality associated with DEN-2 infection. Animal Model: Male BALB/C (8- to 10- week-old) wild-type mice[5] Dosage: 5, 10 and 20 mg/kg Administration: P.o. Result: Dose-dependently inhibited the Zymosan -induced articular hyperalgesia.

[References]

[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.