tcsc0003109 Vofopitant

Vofopitant is potent tachykinin NK₁ receptor antagonist, with pK_is of 10.6, 9.5, and 9.8 for human, rat and ferret NK₁ receptor, respectively.

IC50 & Target: pKi: 10.6 (Human NK₁ receptor), 9.5 (Rat NK₁ receptor), 9.8 (Ferret NK₁ receptor)^[1]

In Vitro: Vofopitant is potent tachykinin NK₁ receptor antagonist, with pK_is of 10.6, 9.5, and 9.8 for human, rat and ferret NK₁ receptor, respectively. Vofopitant less potently inhibits rat 5-HT1A, bovine 5-HT1D, rat 5-HT2A, rat Histamine H1, guinea-pig Histamine H2 and rat Ca²⁺ channel, with pK_is of 6.3, 6.6, 6.5, 6.5, 6.6, and 5.6, respectively. Vofopitant shows negligible affinity at NK₂ and NK₃, with pIC₅₀ of <5.0^[1]. GR205171 (300 µM) potentiates the effects of paroxetine on cortical [5-HT]ext, and inhibits paroxetine-induced increase in [5-HT]ext in the dorsal raphe nucleus^[3].

In Vivo: Vofopitant (GR205171, 30 mg/kg, s.c.) increases the number of choices of the 25-s delayed reward in a T-maze^[2]. Vofopitant (GR205171, 30 mg/kg, i.p.) increases the extracellular 5-HT levels in the frontal cortex of paroxetine-treated wild-type mice, rather than in wild-type mice and paroxetine-treated NK1 receptor knockout mice^[3].