SB-334867 has excellent selectivity for the orexin-1 receptor, blood-brain barrier permeability and shows in vivo activity following ip dosing. SB-334867-A is a non-peptide OX(1) selective receptor antagonist. PKb values are 7.2 and < 5 for inhibition of intracellular Ca2+ release in CHO cells expressing human OX1 and OX2 receptors respectively. SB-334867 blocks orexin-A induced grooming and feeding following systemic administration in vivo. SB-334867-A (OX1, pKB = 7.4; OX2, pKB = 5.7), devoid of appreciable affinity for either 5-HT2B (pKi < 5.3) or 5-HT2C (pKi < 5.4) receptors, provides the first definitive evidence that a central behavioural effect of orexin-A (grooming) is mediated by OX1 receptors.
|Animal models||Male and female Sprague–Dawley rats|
|Formulation||10% (w/v) Encapsin in sterile water|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
1,3-Biarylureas as selective non-peptide antagonists of the orexin-1 receptor.
Porter RA, et al. Bioorg Med Chem Lett. 2001 Jul 23;11(14):1907-10. PMID: 11459658.
SB-334867-A: the first selective orexin-1 receptor antagonist.
Smart D, et al. Br J Pharmacol. 2001 Mar;132(6):1179-82. PMID: 11250867.
Evidence that orexin-A-evoked grooming in the rat is mediated by orexin-1 (OX1) receptors, with downstream 5-HT2C receptor involvement.
Duxon MS, et al. Psychopharmacology (Berl). 2001 Jan 1;153(2):203-9. PMID: 11205420.
A selective orexin-1 receptor antagonist reduces food consumption in male and female rats.
Haynes AC, et al. Regul Pept. 2000 Dec 22;96(1-2):45-51. PMID: 11102651.
|Related OX Receptor Products|
TCS 1102 is a potent, dual orexin receptor antagonist (Ki values are 0.2 and 3 nM for OX2 and OX1 receptors respectively).
MK-3697 is an isonicotinamide small molecule, acting as a potent and selective Orexin 2 receptor antagonist with Ki = 0.95 nM.
SB408124 (Tocris-1963) is a non-peptide antagonist for OX1 receptor with Ki of 57 nM and27 nM in both whole cell and membrane, respectively, exhibits 50-fold selectivity over OX2 receptor.
Suvorexant (MK-4305) is a potent, selective and orally bioavailable antagonist of OX(1)R and OX(2)R for the treatment of insomnia.
MK-6096 is an orally bioavailable potent and selective reversible antagonist of OX(1)R and OX(2)R.
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