SB408124 is a potent and novel nonpeptide?antagonist of orexin-1 (OX(1)) receptor with Ki values of 27 nM and 57 nM in membrane formats and in whole cell, respectively. SB408124 was 50-fold selective over the human OX2?receptor [1].
Pre-treated with SB408124 before orexin A in primary astrocyte cultures from the rat cerebral cortex remarkably decreased the orexin A stimulatory activity on forskolin and basal-induced cAMP production [2].
In rats, SB408124 at dose of 30 μg/10 μl together with orexin-A after histamine (HA) or hypertonic saline injection could prevent the orexin-A-induced reduction in vasopressin (VP) concentration increase [3].
References:
[1] Langmead CJ1,?Jerman JC,?Brough SJ,?Scott C,?Porter RA,?Herdon HJ.Characterisation of the binding of [3H]-SB-674042, a novel nonpeptide antagonist, to the human orexin-1 receptor. Br J Pharmacol.?2004 Jan;141(2):340-6.
[2] Woldan-Tambor A1,?Biegańska K,?Wiktorowska-Owczarek A,?Zawilska JB. Activation of orexin/hypocretin type 1 receptors stimulates cAMP synthesis in primary cultures of rat astrocytes. Pharmacol Rep.?2011;63(3):717-23.
[3] Kis GK1,?Molnár AH,?Daruka L,?Gardi J,?Rákosi K,?László F,?László FA,?Varga C.The osmotically and histamine-induced enhancement of the plasma vasopressin level is diminished by intracerebroventricularly administered orexin in rats. Pflugers Arch.?2012 Apr;463(4):531-6.
