SB-649868

SB-649868 is a potent and selective orally active orexin (OX) 1 and OX₂ receptor antagonist (pK_i =9.4 and 9.5 at the OX₁ and OX₂ receptor, respectively). IC50 & Target: pKi: 9.4 (OX₁), 9.5 (OX₂)^[1] In Vitro: SB-649868 is identified as one the most in vitro potent dual OX₁ and OX₂ receptor antagonist known at that time (pK_i=9.4 and 9.5 at the OX₁ and OX₂ receptor, respectively) ^[1]. SB-649868 antagonizes orexin-A-induced inositol 1 phosphate (IP1) accumulation with the following pK_B value (OX₁=9.67; OX₂=9.64). SB-649868 displaces the [³H]ACT-078573 receptor binding with the following pKi values: OX₁=9.27; OX₂=8.91. Increasing concentrations of SB-649868 (0.3 nM-30 nM) induces a rightward shift of the orexin-A CRCs with a depression of the agonist efficacy suggesting a clear non-surmountable behavior. The calculated apparent pK_b values are 9.67±0.03 and 9.64±0.07 for OX₁ and OX₂^[2].