Vofopitant (dihydrochloride)

Vofopitant dihydrochloride (GR 205171A) is a blood-brain barrier-permeable NK1 receptor inhibitor with a pKi of 9.02 in mice. Vofopitant dihydrochloride blocks vomiting-related responses and inhibits pseudoptyalism. Vofopitant dihydrochloride exerts anxiolytic effects, regulates 5-HT receptor function and increases central 5-HT release. Vofopitant dihydrochloride improves hyperarousal symptoms of post-traumatic stress disorder. Vofopitant dihydrochloride can be used in research related to depression, anxiety, vomiting and postoperative nausea and vomiting^{[1][2][3][4][5][6]}. IC50 & Target:pKi: 9.5 (NK1, rat), 10.6 (NK1, human)^[1] In Vitro:Vofopitant (GR 205171) (10 pM-1 mM; 60 min) dihydrochloride potently inhibits [³H]-SP binding to NK1 receptors in mouse cerebral cortex homogenates with a pK_i of 9.02^[1]. In Vivo:Vofopitant (GR 205171) (3-30 mg/kg; i.p.; single dose) dihydrochloride produces a significant reduction in immobility time at the 30 mg/kg i.p. dose in the mouse forced swim test, with no corresponding change in frontal cortex extracellular monoamine levels^[1].
Vofopitant (GR-205171) (50 µg/kg; i.v.; single dose) dihydrochloride abolishes fictive retching and emesis-associated antral contractility enhancement, reduces emesis-related hypersalivation and parasympathetic nerve activity, but does not affect gastric corpus relaxation, vagosalivary reflex-mediated salivation, or linguosalivary reflex responses in dogs^[2].
Vofopitant (GR 205171) (10 mg/kg; s.c.; single dose) dihydrochloride does not alter DRN serotonergic neuron firing or 5-HT_1A autoreceptor sensitivity in male C57BL/6J mice^[4].
Vofopitant (10 mg/kg/day; s.c.; continuous delivery; 21 days) dihydrochloride reduces the potency of Ipsapirone (HY-19686) to inhibit DRN serotonergic neuron firing by ~1.5-fold, indicating functional desensitization of 5-HT_1A autoreceptors in male C57BL/6J mice^[4].
Vofopitant (10 mg/kg/day; s.c.; continuous delivery; 21 days) dihydrochloride reduces the potency and maximal effect of 5-CT to stimulate [³⁵S]GTP-γ-S binding in the DRN, indicating impaired G-protein coupling of desensitized 5-HT_1A autoreceptors in male C57BL/6J mice^[4].
Vofopitant (10 mg/kg/day; s.c.; continuous delivery; 21 days) dihydrochloride significantly increases basal extracellular 5-HT levels in the DRN and potentiates Paroxetine (HY-122272)-induced cortical 5-HT overflow in male C57BL/6J mice^[4].