VOFOPITANT

pKi: 10.6 (Human NK ₁ receptor), 9.5 (Rat NK ₁ receptor), 9.8 (Ferret NK ₁ receptor)

Vofopitant is potent tachykinin NK ₁ receptor antagonist, with pK _i s of 10.6, 9.5, and 9.8 for human, rat and ferret NK ₁ receptor, respectively. Vofopitant less potently inhibits rat 5-HT1A, bovine 5-HT1D, rat 5-HT2A, rat Histamine H1, guinea-pig Histamine H2 and rat Ca ²⁺ channel, with pK _i s of 6.3, 6.6, 6.5, 6.5, 6.6, and 5.6, respectively. Vofopitant shows negligible affinity at NK ₂ and NK ₃ , with pIC ₅₀ of <5.0. 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.

Vofopitant (GR205171, 30 mg/kg, s.c.) increases the number of choices of the 25-s delayed reward in a T-maze. 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.