MK-0249

MK-0249 (Compound 1) is a potent, selective and orally active histamine H₃ receptor antagonist, with an IC₅₀ of 1.7 nM for human H3^[1]. IC50 & Target: Ki: 1.7 nM (Human H3)^[1] In Vitro: MK-0249 (Compound 1) shows very good hepatic clearance values (CLh e 11 mL/min/kg), and is a substrate for rat P-gp but not for human P-gp^[1].
MK-0249 displays potent binding affinity to human, rat, and rhesus H₃ receptors with K_i values of 6.8 ± 1.3 nM, 33 ± 3 nM, and 4.3 ± 1.2 nM, respectively^[1].
MK-0249 shows high intrinsic activity^[1]. In Vivo: MK-0249 (Compound 1) (0-30 mg/kg; p.o.; once) elevates histamine levels in the rat brain in a dose-dependent manner^[1].
MK-0249 (10 mg/kg; p.o.; once) shows markedly higher brain penetrability and a lower plasma Occ90 value in mdr1a (-/-) mice than in mdr1a (+/+) mice^[1].
MK-0249 shows rodent brain permeability and is significantly limited by P-gp mediated efflux in rodents, whereas the extent of P-gp mediated efflux in humans should be very small or negligible^[1].