Vofopitant (GR 205171) is a potent NK1 receptor antagonist with anxiolytic and antiemetic activity for the study of post-traumatic stress disorder (PTSD).

NK1R (rat):9.5 (pKi), NK1R (ferret):9.8(pKi), NK1R (human):10.6 (pKi)

Co-administration of paroxetine (4 mg/kg; i.p.) with the NK1 receptor antagonists, Vofopitant/GR205171 (30 mg/kg; i.p.) or L733060 (40 mg/kg; i.p.), potentiated the effects of paroxetine on cortical [5-HT]ext in wild-type mice, whereas GR205171 (30 mg/kg; i.p.) had no effect on paroxetine-induced increase in cortical [5-HT]ext in NK1 receptor knock-out mice. When GR205171 (300 micro mol/L) was perfused by 'reverse microdialysis' into the dorsal raphe nucleus, it potentiated the effects of paroxetine on cortical [5-HT]ext, and inhibited paroxetine-induced increase in [5-HT]ext in the dorsal raphe nucleus[2].

In a T-maze experiment, Vofopitant (GR205171, 30 mg/kg, subcutaneously) enhances the selection of a 25-second delayed reward[3]. Furthermore, when administered intraperitoneally at the same dosage, Vofopitant elevates extracellular serotonin (5-HT) levels in the frontal cortex of wild-type mice treated with paroxetine, but not in untreated wild-type or in NK1 receptor knockout mice also treated with paroxetine[2].