SB408124 is a non-peptide antagonist for OX1 receptor with Ki of 57 nM and 27 nM in both whole cell and membrane, respectively, exhibits 50-fold selectivity over OX2 receptor.

OX1 (membrane):27 nM(Ki), OX1 (whole cell):57 nM(Ki)

SB-408124 binds hypocretin type 1 receptor (HcrtR1) with pKi values of 7.57. Calcium mobilization studies shows that SB-408124 is a functional antagonist of the OX1 receptor with a affinity of approximately 50-fold selectivity over the OX2 receptor. [1] A recent study indicates that pretreatment of primary cultures of rat astrocytes with SB-401824 before Orexin A administration significantly reduced the stimulatory action of Orexin A on both basal and forskolin-acivated cAMP production. [2]

SB-408124 (30 μg/10 μL, administered intracerebroventricularly) reduces Orexin-A-induced water intake in Wistar rats. Intracerebroventricular Orexin-A (30 μg/10 μL) inhibits vasopressin increase induced by histamine or 2.5% NaCl, and this effect is moderated by pretreatment with SB-408124. Intracerebroventricular pretreatment with SB-408124 (50 mM, 5 μL/h) prevents Bicuculline (BIC)-induced increases in endogenous glucose production (EGP). [3] [4]