(±)-Fabesetron

(±)-Fabesetron ((±)-FK1052 free base) is the racemate of Fabesetron, which is a potent 5-HT3 and 5-HT4 receptor dual antagonist^[1]. IC50 & Target:5-HT3 and 5-HT4 receptor^[1] In Vivo: In conscious rats, both 5-HT and 5-methoxytryptamine significantly increase fecal pellet output and accelerate colonic transit. In contrast, the effect of 2-methyl-5-HT is slight. Although Ondansetron and Granisetron slightly reduce 5-HT (1 mg/kg s.c.) stimulated colonic transit, FK1052, at 0.1 mg/kg p.o., inhibits completely the increases in the colonic transit. Furthermore, FK1052, Ondansetron and Granisetron significantly depress the increase in fecal pellet output caused by wrap-restraint stress, with ED₅₀ values of 0.21, 3.0 and 1.1 mg/kg p.o., respectively. Intraperitoneal administration of 5-HT and 5-methoxytryptamine, but not 2-methyl-5-HT, produces a dose-related increase in the incidence of diarrhea in fasted mice. 5-HT (0.32 mg/kg i.p.)-induced diarrhea is also inhibited by FK1052, Ondansetron and Granisetron, with ED₅₀ values of 0.09, 2.3 and 0.88 mg/kg p.o., respectively^[1]. FK1052 (1 mg/kg i.v. ×4) apparently reduces delayed emesis caused by Methotrexate (MTX) and increases, but not significantly, the time for onset of emesis. Furthermore, increasing the dose to 3.2 mg/kg of FK1052 also significantly inhibits the number of the emetic episodes induced by MTX, of which the action is more effective than the treatment with FK1052 at 1 mg/kg^[2].