Cell lines

CHO-OX1 and CHO-OX2 cells

Preparation method

The solubility of this compound in DMSO is >5.2mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

100 pM-10 μM

Applications

In CHO-OX1 cells, SB-334867-A (100 pM-10 μM) inhibited the orexin-A (10 nM) and orexin-B (100 nM)-induced calcium responses in a concentration-dependent way, with apparent pKB values of 7.27±0.04 and 7.23±0.03, respectively. In CHO-OX2 cells, SB-334867-A also inhibited the orexin-A (10 nM) and orexin-B (10 nM)-induced calcium responses by 32.7±1.9 and 22.0±4.0%, respectively.

Animal models

adult male Lister hooded rats

Dosage form

3.0, 10.0 and 30.0 mg/kg, i.p.

Application

In adult male Lister hooded rats, SB-334867 significantly reduced food intake and most active behaviours (eating, grooming, sniffing, locomotion and rearing), while increasing resting. SB-334867 dose-dependently blocked the effects of orexin-A, such as stimulation of food intake, increasing grooming and delaying the onset of behavioural satiety.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

SB-334867 is a selective antagonist of orexin-1 receptor [1].

Orexin-A and orexin-B are two peptides isolated from rat hypothalamus. They are involved in some physiological functions such as the control of feeding, energy metabolism and regulation of the sleep-wake cycle. SB-334867 can inhibit the orexin-A and orexin-B induced calcium responses in CHO-OX1 cells with pKB values of 7.27 and 7.23, respectively. SB-334867 is more selective for OX1 receptor over OX2 receptor. It causes 32.7% and 22% inhibition of orexin-A and orexin-B induced calcium responses in CHO-OX2 cells, respectively. Moreover, SB-334867 is found to reduce both orexin-A-induced and fasting-induced food intake. The acute anorectic effect of it is associated with signi(R)cant reductions in all active behaviours [1, 2].

References:
[1] Smart D, Sabido-David C, Brough S J, et al. SB-334867-A: the first selective orexin-1 receptor antagonist. British journal of pharmacology, 2001, 132(6): 1179-1182.
[2] Rodgers R J, Halford J C G, Nunes de Souza R L, et al. SB-334867, a selective orexin-1 receptor antagonist, enhances behavioural satiety and blocks the hyperphagic effect of orexin-A in rats. European Journal of Neuroscience, 2001, 13(7): 1444-1452.