Navafenterol

Navafenterol?(AZD-8871)?is an inhaled dual-acting, potent, selective, and long-lasting M3-antagonist/β2-agonist (MABA) with long-lasting effects and favorable safety profile. The pIC₅₀ is 9.5 for human M3?receptor, and the pEC₅₀ is 9.5 for β2-adrenoceptor. Navafenterol can be used for the research of chronic obstructive pulmonary disease (COPD).?Bronchoprotective and antisialagogue effects. Favorable cardiovascular profile^[1]. In Vitro: The pIC₅₀?values of Navafenterol?(AZD-8871) at the human M1, M2, M3, M4, and M5?receptor are 9.9, 9.9, 9.5, 10.4, and 8.8, respectively^[1].
pEC₅₀?values of Navafenterol at theβ1, β2, and β3 adrenoceptor are 9.0, 9.5, and 8.7, respectively. It is selective for the?β2-adrenoceptor over the?β1?and?β3?subtypes (3- and 6-fold, respectively)^[1].
Navafenterol shows kinetic selectivity for the M3?(half-life: 4.97 hours) over the M2?receptor (half-life: 0.46 hour)^[1].
Navafenterol?shows dual antimuscarinic and?β2-adrenoceptor functional activity in isolated guinea pig tissue (pIC₅₀?in electrically stimulated trachea: 8.6; pEC₅₀?in spontaneous tone isolated trachea: 8.8, respectively), which are sustained over time^[1]. In Vivo: Navafenterol?(AZD-8871) prevents acetylcholine-induced bronchoconstriction in both guinea pig and dog with minimal effects on salivation and heart rate at doses with bronchoprotective activity. Moreover, AZD8871 shows long-lasting effects in dog, with a bronchoprotective half-life longer than 24 hours. Navafenterol?shows dose-proportional bronchoprotective effect, with a nonsignificantly different potency (ID₄₀?of 0.40 μg/kg)^[1].