Orexin receptor agonist Yan 7874 is a weak agonist of orexin/hypocretin receptors and shows orexin receptor-independent cytotoxicity

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Orexin receptor agonist Yan 7874 is a weak agonist of orexin/hypocretin receptors and shows orexin receptor-independent cytotoxicity

Two promising lead structures of small molecular orexin receptor agonist have been reported, but without detailed analyses of the pharmacological properties. One of them, 1-(3,4-dichlorophenyl)-2-[2-imino-3-(4-methylbenzyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl]ethan-1-ol (Yan 7874), is commercially available, and we set out to analyze its properties. As test system we utilized human OX1 and OX2...

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Suvorexant, a dual orexin receptor antagonist, protected seizure through interaction with GABAA and glutamate receptors

Orexin can increase neuronal excitability and induce epileptic activity. In this study, the effects of suvorexant (orexin receptor antagonist) on pentylenetetrazol (PTZ) and maximal electroshock (MES)-induced seizure were investigated. Mice were divided into 5 groups of six animals each including normal saline (10 ml/kg), diazepam (2 mg/kg) and suvorexant (50, 100 and 200 mg/kg) groups. In PTZ ...

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Suvorexant, a dual orexin receptor antagonist, protected seizure through interaction with GABAA and glutamate receptors

Orexin can increase neuronal excitability and induce epileptic activity. In this study, the effects of suvorexant (orexin receptor antagonist) on pentylenetetrazol (PTZ) and maximal electroshock (MES)-induced seizure were investigated. Mice were divided into 5 groups of six animals each including normal saline (10 ml/kg), diazepam (2 mg/kg) and suvorexant (50, 100 and 200 mg/kg) groups. In PTZ ...

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Orexin and Orexin Receptors

“Reverse pharmacology”, i.e., ligand identification using cell lines expressing orphan receptors, combined with genetic engineering techniques, has increased our understanding of novel signaling systems in the body. Orexin is the first and most successful example of the factors to which such an approach was applied. Our group initially identified orexin A and orexin B as endogenous peptide liga...

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Orexin directly excites orexin neurons through orexin 2 receptor.

Orexin neurons (hypocretin neurons) have a critical role in the regulation of sleep/wakefulness, especially in the maintenance of arousal. Here, we revealed that orexin neurons are directly and indirectly activated by orexin via the orexin 2 receptor (OX2R). Orexin B (1 μM) induced depolarization in orexin neurons, which was still observed in the presence of TTX (1 μM), AP-5 (50 μM), and CNQX (...

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ژورنال

عنوان ژورنال: PLOS ONE

سال: 2017

ISSN: 1932-6203

DOI: 10.1371/journal.pone.0178526