| Description | Orvepitant maleate is an effective, selective, and well-tolerated neurokinin-1 receptor (NK-1) antagonist (pKi: 10.2 for human neurokinin-1 receptor). Orvepitant maleate has the potential for depressive disorder and chronic refractory cough (CRC) treatment. Orvepitant maleate can across the blood-brain barrier. |
| In vitro | Orvepitant (0.3-10 nM), pre-incubated for 1 h at 37℃ before adding the agonist SP, produces a non-surmountable antagonism of agonist concentration-response curve. For the Orvepitant apparent pKB value is 10.30. Orvepitant is further characterized in terms of the ability to functionally inhibit substance P (SP)-induced release of cytosolic Ca2+ in human neurokinin-1 receptor (hNK1)-CHO cells [1]. |
| In vivo | Orvepitant shows an oral bioavailability (F) of 17% in rat and 55% in a dog, plasma clearance (Clp) of 29 mL/min/kg in rat and 6 mL/min/kg in dog and a half-life of 2.3 h in rat and 6.1 h in the dog. Orvepitant (0.3-10 mg/kg; p.o.; marmoset) treatment displays a dose-dependent reduction of the number of postures was observed at 1 mg/kg (34.9% reduction), 3 mg/kg (36.6% reduction) and 10 mg/kg (46.4% reduction), suggesting a potential anxiolytic-like effect of the compound. As far as the brain penetration in rats is concerned, a B/P ratio of 1.2 is observed 5 min after the i.v. administration of a 1 mg/kg dose of Orvepitant[1]. |
| Target activity | NK1:10.2 （pki） |
| Synonyms | GW823296 maleate |
| molecular weight | 744.7 |
| Molecular formula | C35H39F7N4O6 |
| CAS | 579475-24-4 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| References | 1. Di Fabio R, et al. Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate. Bioorg Med Chem. 2013 Nov 1;21(21):6264-73. 2. Smith J, et al. The Neurokinin-1 Receptor Antagonist Orvepitant Is a Novel Antitussive Therapy for Chronic Refractory Cough: Results From a Phase 2 Pilot Study (VOLCANO-1). Chest. 2020 Jan;157(1):111-118. |