Vofopitant_product_DataBase

Bioactivity

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

Target

pKi: 10.6 (Human NK1 receptor), 9.5 (Rat NK1 receptor), 9.8 (Ferret NK1 receptor)

Invitro

Vofopitant is potent tachykinin NK1 receptor antagonist, with pKis 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 pKis 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].

Name

Vofopitant

CAS

168266-90-8

Formula

C21H23F3N6O

Molar Mass

432.44

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Reference

[1]. Gardner CJ, et al. GR205171: a novel antagonist with high affinity for the tachykinin NK1 receptor, and potent broad-spectrum anti-emetic activity. Regul Pept. 1996 Aug 27;65(1):45-53. [2]. Loiseau F, et al. Antidepressant-like effects of agomelatine, melatonin and the NK1 receptor antagonist GR205171 in impulsive-related behaviour in rats. Psychopharmacology (Berl). 2005 Oct;182(1):24-32. Epub 2005 Sep 29. [3]. Guiard BP, et al. Blockade of substance P (neurokinin 1) receptors enhances extracellular serotonin when combined with a selective serotonin reuptake inhibitor: an in vivo microdialysis study in mice. J Neurochem. 2004 Apr;89(1):54-63.

PeptideDB

Vofopitant

CAS: 168266-90-8 F: C21H23F3N6O W: 432.44