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SB-408124 Hydrochloride is a selective non-peptide orexin receptor 1 (OX1) receptor antagonist with K_is of 57 nM and 27 nM in whole cell and membrane, respectively. SB-408124 Hydrochloride exhibits 50-fold selectivity over OX2 receptor.

Primary neuronal cultures from the hypothalamus of newborn SD rats are incubated with orexin A (1 µM), orexin A (1 µM) together with SB-408124 (100 µM) for 6 h. Orexin A-induced increases in arginine vasopressin (AVP) mRNA levels (2.7-fold) are attenuated by SB-408124 (1.2-fold).

SB-408124 reduces anxiety after psychotraumatic exposure. Predator induces acute psychotraumatic exposure decrease corticoliberin level in the rat's amygdala. Intranasal administration of SB-408124 restores it closely to normal and has an anxiolytic effect on animal behaviour.
Bilateral paraventricular nucleus microinjection of SB-408124 (30 pmol/50 nL per side) results in a greater reduction in mean arterial pressure (MAP) in high-salt intake (-16 mmHg) compared with NS-fed (-4 mmHg) anesthetized Dahl salt-sensitive rats.

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