P2X3 antagonist 34 is a potent, selective and orally active P2X3 homotrimeric receptor antagonist with IC 50 s of 25 nM, 92 nM and 126 nM for human P2X3 , rat P2X3 and guinea pig P2X3 receptors , respectively. P2X3 antagonist 34 is less active against human, rat and guinea pig P2X2/3 heterotrimeric receptors. P2X3 antagonist 34 has strong anti-tussive effect
In Vitro
P2X3 antagonist 34 (BLU-5937; 500 nM) is able to block αβ-meATP-induced sensitization and firing activity of isolated primary nociceptors in rat dorsal root ganglions (DRGs), through P2X3 homotrimeric receptor antagonism. The sensitizing effect of αβ-meATP and the inhibition of P2X3 antagonist 34 are reversible after washout. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
P2X3 antagonist 34 (BLU-5937; 0.3-0 mg/kg, oral administration; male Dunkin Hartley guinea pigs) treatment significantly reduces the histamine-induced enhancement in the number of citric acid-induced coughs in a dose-dependent fashion in a guinea pig cough model . P2X3 antagonist 34 (BLU-5937; 3 and 30 mg/kg, oral) is also shown to reduce significantly and dose-dependently the ATP-induced enhancement of citric acid-induced coughs in the guinea pig . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male Dunkin Hartley guinea pigs Dosage: 0.3 mg/kg, 3 mg/kg, 30 mg/kg Administration: Oral administration Result: Significantly reduced the histamine-induced enhancement in the number of citric acid-induced coughs in a dose-dependent fashion.
