CP 99,994 (hydrochloride)

CP 99,994 is a nonpeptide neurokinin-1 (NK₁) receptor antagonist (K_i = 0.25 nM in a radioligand binding assay).¹ It is selective for NK₁ over NK₂ and NK₃ receptors (K_is = >10 μM for both) as well as dopamine D₁ and D₂, α₁-, α₂- and β-adrenergic, serotonin, histamine H₁, muscarinic and nicotinic acetylcholine, μ-opioid, glutamate, benzodiazepine, and γ-aminobutyric acid (GABA) receptors (IC₅₀s = >1 μM for all). In vitro, CP 99,994 inhibits excitation of guinea pig locus coeruleus cells induced by substance P (Item No. 24035; IC₅₀ = 25 nM). It inhibits increases in horizontal locomotor activity induced by the NK₁ agonist [Sar⁹,Met(O₂)¹¹]-substance P in guinea pigs (ID₅₀ = 0.59 mg/kg). CP 99,994 inhibits aerosolized capsaicin-induced plasma extravasation in guinea pig lung (ID₅₀ = 4 mg/kg). It exhibits anti-emetic effects in ferret models of emesis induced by copper sulfate, loperamide, or cisplatin (Item No. 13119) when administered at doses of 0.3 and 1 mg/kg.²

WARNING This product is not for human or veterinary use.

1. McLean, S., Ganong, A., Seymour, P.A., et al. Pharmacology of CP-99,994; a nonpeptide antagonist of the tachykinin neurokinin-1 receptor. J. Pharmacol. Exp. Ther. 267(1), 472-479 (1993).

2. Watson, J.W., Gonsalves, S.F., Fossa, A.A., et al. The anti-emetic effects of CP-99,994 in the ferret and the dog: Role of the NK1 receptor. Br. J. Pharmacol. 115(1), 84-94 (1995).