PF-03654764

PF-03654764 is an orally active, selective histamine H₃ receptor antagonist with K_i values of 1.2 nM and 7.9 nM for human H₃ and rat H₃ in whole cell assay, respectively. The combination of PF-03654764 and Fexofenadine (HY-B0801A) has the potential for allergic rhinitis research^[1][2]. In Vitro: PF-03654764 has pK_i values of 8.98 and 8.10 for human H₃ and rat H₃ in whole cell assay, respectively. PF-03654764 has pK_i values of 8.84, 7.73 and K_i values of 1.4 nM and 19 nM for human H₃ and rat H₃ in HEK-293 cells, respectively. PF-03654764 has >1000-fold selectivity for the H3 receptor over the other histamine receptor subtypes^[1].
PF-03654764 has a human liver microsomes (HLM) T_1/2 of 120 min and a HLM CL_h <5 mL/min?kg^[1].
In Vivo: PF-03654764 (10 mL/kg; oral; 14 days) has a C_max of 8057 ng/mL and an AUC_0-24 of 67400 ng?h/mL in Sprague-Dawley rats^[1].
PF-03654764 (1 mL/kg; oral; 7 days) has a C_max of 6302 ng/mL and an AUC_0-24 of 18175 ng?h/mL in beagle dogs^[1].