SB-334867-A is the first selective and non-peptide orexin-1 receptor antagonist with pKB values of 7.27 and 7.23 for inhibition of the orexin-A (10 nM) and orexin-B (100 nM)-induced calcium responses, respectively, but had no effect on the UTP (3μM)-induced calcium response in CHO-OX1 cells. SB-334867-A inhibited OX2 mediated calcium responses up to 10μM. A single intraperitoneal injection with SB-334867-A at dose of 30mg/kg during the light phase reduced both orexin-A-induced food intake and feeding stimulated by an overnight fast for 4h in male rats. Daily injections with SB-334867-A at the start of the dark phase for 3 days reduced natural feeding in male rats over 24 h on day 1 and day 3. SB-334867-A possesses blood–brain barrier permeability shown as CNS penetration ratio brain/blood ratio of 0.4:1.
SB-334867 free base 细胞实验
Cell Line
Concentration
Treated Time
Description
References
CeA neurons
10 μM
SB-334867 significantly decreased sIPSC frequency in CeA neurons from LgA rats, indicating that HCRT-R1 regulates basal CeA GABA release in LgA rats.
Biol Psychiatry. 2017 Apr 1;81(7):606-615.
SB-334867 free base 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Intracerebral hemorrhage model
Intraperitoneal injection
10 mg/ml
Once, 1 hour after ICH
To study the neuroprotective mechanism of OXA, it was found that SB-334867 (OXR1 antagonist) had no significant effect on the anti-inflammatory effect of OXA
J Neuroinflammation. 2020 Jun 15;17(1):187
Sprague-Dawley rats
Cocaine self-administration model
Intracranial microinjection
1 mM
Single injection, immediately before testing
To investigate the effect of SB-334867 in VTA on cue-driven motivation for cocaine. Results showed that SB-334867 reduced motivation only when animals were exposed to cocaine-associated cues during training and testing.
Neuropsychopharmacology. 2022 Feb;47(3):741-751
Mice
Morphine-induced sensitization to locomotor activity model
Intraperitoneal injection
20 mg/kg
Administered 15 min before morphine injection, 5 times, with 3-day intervals
SB-334867 inhibited the acquisition of morphine-induced sensitization to locomotor activity and significantly altered the mRNA expression of orexin, dopamine, and adenosine receptors, as well as the expression of GFAP and Iba-1 in the brain.
Mol Neurobiol. 2018 Nov;55(11):8473-8485
Rats
Fentanyl self-administration model
Intraperitoneal injection
3, 10, or 30 mg/kg
Administered 30 min prior to testing, with a minimum of 3 days between tests
SB-334867 increased demand elasticity (decreased motivation) for fentanyl without affecting consumption at null cost. Baseline α values predicted SB efficacy, with SB being most effective in highly motivated animals. SB also attenuated cue-induced reinstatement of fentanyl seeking.
OX1R signaling plays a particular role in promoting compulsive-like alcohol drinking, and low doses of SB-334867 significantly reduced compulsive-like alcohol consumption
Neuropharmacology. 2016 Nov;110(Pt A):431-437
Mice
Restraint stress model
Intraperitoneal injection
15 mg/kg
Single injection, lasting 30 minutes
To investigate the effect of SB-334867 on restraint stress-induced analgesia, results showed that SB-334867 significantly inhibited the restraint stress-induced analgesia.
Neuropharmacology. 2016 Jun;105:577-586
Rats
Adult male Sprague Dawley rats
Intraperitoneal injection
1 mg/kg
Single dose
To assess the effect of SB-334867 on the hypoxic ventilatory response, results showed that SB-334867 significantly reduced the hypoxic ventilatory response.
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