SB-408124 Hydrochloride 

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^[1].

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)^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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^[2].
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^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

392.83

C₁₉H₁₉ClF₂N₄O

1431697-90-3

Solid

White to gray

O=C(NC1=CC=C(C=C1)N(C)C)NC2=CC(C)=NC(C2=CC(F)=C3)=C3F.[H]Cl

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

• [1]. Langmead et al (2004) Characterisation of the binding of [3H]-SB-674042, a novel nonpeptide antagonist, to the human orexin-1 receptor. Br.J.Pharmacol. 141 340.

  [2]. I Tissen, et al. OX1R ANTAGONIST SB408124 ACTION AND EXTRAHYPOTHALAMIC CRF IN RATS AFTER PSYCHOTRAUMATIC EXPOSURE. Georgian Med News. 2019 May;(290):127-131.  [Content Brief]

  [3]. Michael J Huber, et al. Increased activity of the orexin system in the paraventricular nucleus contributes to salt-sensitive hypertension. Am J Physiol Heart Circ Physiol. 2017 Dec 1;313(6):H1075-H1086.  [Content Brief]