SB-408124 Hydrochloride

• CAT Number: I001664
• CAS Number: 1431697-90-3
• Molecular Formula: C19H19ClF2N4O
• Molecular Weight: 392.83
• Purity: ≥95%
• Synonyms: 1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea;hydrochloride
• InChI: InChI=1S/C19H18F2N4O.ClH/c1-11-8-17(15-9-12(20)10-16(21)18(15)22-11)24-19(26)23-13-4-6-14(7-5-13)25(2)3;/h4-10H,1-3H3,(H2,22,23,24,26);1H
• InChIKey: DIHXPSGMLOETTI-UHFFFAOYSA-N
• SMILES: CC1=CC(=C2C=C(C=C(C2=N1)F)F)NC(=O)NC3=CC=C(C=C3)N(C)C.Cl

SB-408124 Hydrochloride is a selective non-peptide orexin receptor 1 (OX1) receptor antagonist with Kis 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].
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].

Reference

[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.
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[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.
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