CAS No.: 249889-64-3
Inquire SB-334867 (cas: 249889-64-3 ) online by filling out the inquiry form, we will get back to you within 24 hours!
For research use only. Not Intended for Therapeutic Use!
SB-334867; SB 334867; SB334867;1-(2-methyl-1,3-benzoxazol-6-yl)-3-(1,5-naphthyridin-4-yl)urea
|Description:||SB-334867(cas 249889-64-3) is a selective non-peptide orexin OX1 receptor antagonist with a pKb value of 7.2. SB-334867 inhibited the orexin-A (10 nM) and orexin-B (100 nM)-induced calcium responses (pK(B)=7.|
We would like to match the lowest price on market if possible.
SB-334867(cas 249889-64-3) is a selective non-peptide orexin OX1 receptor antagonist with a pKb value of 7.2. SB-334867 inhibited the orexin-A (10 nM) and orexin-B (100 nM)-induced calcium responses (pK(B)=7.27+/-0.04 and 7.23+/-0.03 respectively, n=8), but had no effect on the UTP (3 microM)-induced calcium response in CHO-OX(1) cells. SB-334867-A (10 microM) also inhibited OX(2) mediated calcium responses (32.7+/-1.9% versus orexin-A). Single-unit recordings in anesthetized rats demonstrated the central effects of the selective orexin-1 receptor antagonist SB-334867 (2 mg/kg, intravenous), as it reversed the excitatory effects of orexin-A administration (6 microg, intracerebroventricular) on the activity of locus coeruleus (LC) cells. The ICV injection of SB-334867 alone had no effect on the formalin-induced nociceptive behaviors. Pre-treatment with SB-334867 at a dose of 0.5 nmol significantly attenuated the analgesia induced by morphine (at dose 1.5mg/kg of morphine; interphase and phase 2B and at dose 3mg/kg of morphine just phase 2B of formalin test). Administered alone, SB-334867 (30 mg/kg, but not lower doses) significantly reduced food intake and most active behaviours (eating, grooming, sniffing, locomotion and rearing), while increasing resting. Pretreatment with SB-334867 dose-dependently blocked these effects of orexin-A, with significant antagonism evident at dose levels (3-10 mg/kg) below those required to produce intrinsic behavioural effects under present test conditions in rats.
Appearance:white to off-white solid powder
1. Life Sci. 2016 Apr 1;150:81-8. doi: 10.1016/j.lfs.2016.02.075. Epub 2016 Feb 23.
SB 334867, a selective orexin receptor type 1 antagonist, elevates seizure
threshold in mice.
Socała K(1), Szuster-Ciesielska A(2), Wlaź P(3).
(1)Department of Animal Physiology, Institute of Biology and Biochemistry, Maria
Curie-Skłodowska University, Lublin, Poland. Electronic address: [email protected]
(2)Department of Virology and Immunology, Institute of Microbiology and
Biotechnology, Maria Curie-Skłodowska University, Lublin, Poland.
(3)Department of Animal Physiology, Institute of Biology and Biochemistry, Maria
Curie-Skłodowska University, Lublin, Poland.
AIM: Orexins A and B are hypothalamic neuropeptides involved in a number of
physiological and behavioral processes. They work via OX1 and OX2 receptors.
Recent studies revealed that orexins may be implicated in seizure activity.
Therefore, the present study was undertaken to evaluate the influence of SB
334867 (a selective OX1 receptor antagonist) and EMPA (a selective OX2 receptor
antagonist) on the seizure thresholds in mice. We also aimed to determine the
changes of orexin A level following different types of seizures.
MAIN METHODS: The intravenous pentylenetetrazole (i.v. PTZ) seizure test, the
maximal electroshock seizure threshold (MEST) test and the 6 Hz seizure test were
used in the present study. Brain orexin A level was determined via enzyme-linked
KEY FINDINGS: SB 334867 did not affect the seizure threshold for myoclonic
twitches and tonic seizures in the i.v. PTZ seizure test. This compound, however,
significantly raised the threshold for the PTZ-induced clonic seizures, for tonic
hindlimb extension in the MEST test as well as for psychomotor seizures induced
by 6 Hz stimulation. In comparison, EMPA did not alter the seizure thresholds in
the i.v. PTZ test. Both EMPA and SB 334867 did not affect motor coordination and
muscular strength. ELISA showed the increase of total brain orexin A level
following different types of seizures.
SIGNIFICANCE: Our results provide further evidence for the role of orexins in
seizure activity and suggest that pharmacological blockade of the OX1 receptors
may represent a novel therapeutic approach in the treatment of seizure disorders.
2. Behav Pharmacol. 2011 Apr;22(2):173-81. doi: 10.1097/FBP.0b013e328343d761.
Orexin-1 receptor antagonist SB-334867 reduces the acquisition and expression of
cocaine-conditioned reinforcement and the expression of amphetamine-conditioned
Hutcheson DM(1), Quarta D, Halbout B, Rigal A, Valerio E, Heidbreder C.
(1)Department of Biology, Neurosciences CEDD, GlaxoSmithKline Medicines Research
Centre, Verona, Italy.
Preclinical evidence suggests an important role of the brain orexin system in
behaviours related to drug addiction. This study aimed at assessing the effect of
the orexin-1 receptor antagonist SB-334867 on aspects of
psychostimulant-conditioned behaviours that are thought to contribute to the
maintenance of and relapse to psychostimulant drug use. Rats were first allowed
to nose poke for cocaine infusions associated with a cue light presentation
(conditioned stimulus; CS) over five daily sessions. Subsequently, drug-free rats
were tested for the acquisition of a new response in which presses on a novel
active lever led to the presentation of the previously paired CS. We tested
SB-334867 in two conditions, SB-334867 was given either before each cocaine
self-administration or before the initial four sessions of acquisition for a
novel instrumental responding paired with the CS (conditioned reinforcement). The
effect of SB-334867 was also tested on the expression of conditioned place
preference to d-amphetamine. The rats treated with SB-334867 before each cocaine
self-administration session subsequently showed reduced active lever pressing
compared with controls in the initial days of the conditioned reinforcement. In
the second study, untreated rats showed normal acquisition of discriminated
responding preferential for the lever providing the cocaine cue. In contrast,
SB-334867 decreased the number of active lever pressing (compared with the
control) with significant effects in all sessions. Finally, SB-334867 blocked the
expression of d-amphetamine-induced conditioned place preference. These results
suggest that orexin-1 receptor antagonism could offer therapeutic potential in
reducing the impact of psychostimulant-predictive stimuli that contribute to
compulsive drug seeking in human drug users.
3. Br J Pharmacol. 2008 May;154(2):406-16. doi: 10.1038/bjp.2008.3. Epub 2008 Jan
Differential effects of the hypocretin 1 receptor antagonist SB 334867 on
high-fat food self-administration and reinstatement of food seeking in rats.
Nair SG(1), Golden SA, Shaham Y.
(1)Behavioral Neuroscience Branch, NIDA/IRP/NIH/DHHS, Baltimore, MD 21224, USA.
BACKGROUND AND PURPOSE: Many studies have demonstrated a role of hypocretin 1
(orexin 1) receptors in home-cage food consumption in rodents. However, the role
of these receptors in operant food self-administration or relapse to food seeking
in animal models is unknown.
EXPERIMENTAL APPROACH: In Experiment 1, we trained food-restricted rats (16-20 g
per day) to lever press for high-fat (35%) pellets (3-6 h per day, every other
day). We then tested the effect of the hypocretin 1 receptor antagonist SB 334867
(10, 20 mg kg(-1), i.p) on pellet self-administration. In Experiment 2, we
trained rats to self-administer the food pellets, and following extinction of the
food-reinforced responding, we tested the effect of hypocretin 1 (3 and 6 mug,
i.c.v) on reinstatement of food-seeking and the effect of SB 334867 on this
reinstatement. In Experiment 3, we tested the effect of SB 334867 on
reinstatement induced by non-contingent pellet exposure (pellet-priming) or the
pharmacological stressor yohimbine (2 mg kg(-1), i.p).
KEY RESULTS: SB 334867 attenuated high-fat pellet self-administration. In
contrast, SB 334867 had no effect on reinstatement of lever presses induced by
hypocretin 1, pellet-priming or yohimbine.
CONCLUSIONS AND IMPLICATIONS: These data indicate that during dieting, hypocretin
1 receptors contribute to operant high-fat pellet self-administration, but not to
relapse to food seeking induced by acute re-exposure to the food itself or by the
induction of a stress-like state.
Class: Benzoxazoles; Obesity therapies; Urea compounds
Mechanism of Action: Orexin receptor antagonists
Orphan Drug Status: No