Casopitant mesylate (GW679769B) is a potent, selective, brain permeable and orally activeneurokinin 1 (NK1) receptorantagonist. Casopitant mesylate is a second in the class of antiemetics that acts to antagonise the emetogenic effect of substance P. Casopitant mesylate is also a substrate and a weak-to-moderate inhibitor ofCYP3A4. Casopitant mesylate can be used for chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV)^[1][2].

In a ferret-model of Cisplatin- induced emesis, Casopitant (GW679769) inhibits retching and vomiting and reduced nausea-like behaviours in a dose-dependent manner. The pharmacokinetics and brain penetration of casopitant are studied in the ferret-model of cisplatin-induced emesis. Following a single intraperitoneal dose, radioactive labeled Casopitant ([¹⁴C]Casopitant) is rapidly absorbed, with plasma and brain concentrations being approximately equal at two hours post-dosing. [¹⁴C]Casopitant is found in the brain as the parent compound and two major oxidative metabolites (M1 and M2), accounting for approximately 76%, 19%, and 3% of the radioactivity, respectively; suggesting that the pharmacologic activity of Casopitant in the ferret is largely attributable to the parent compound. Casopitant possesses a high affinity for brain NK1 receptors in the ferret^[2].

712.72

Solid

C₃₁H₃₉F₇N₄O₅S

414910-30-8

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)