Orexin Receptor Data

View Orexin Receptors

Receptor Subtype	OX₁ Receptors	OX₂ Receptors

G protein	G_q/11	G_q/11
Transduction Mechanism	↑ PLC → ↑ Ca²⁺ influx	↑ PLC → ↑ Ca²⁺ influx
Primary Locations	Ventromedial hypothalamus, locus coeruleus, median raphe, hippocampus, tenia tecta	Cerebral cortex (layers IV-VI), medial hypothalamus, paraventricular hypothalamus, nucleus accumbens, subthalamic and paraventricular thalamus, anterior pretectal nucleus
Likely Physiological Roles	Sleep-wakefulness, energy homeostasis	Sleep-wakefulness

Key Compounds	K_i Values (nM)

Orexin A (human, rat, mouse) (1455)	20	38
Orexin B (human) (1456)	420	36
SB 334867 (1960)	7.2*	< 5*
SB 408124 (1963)	21.7^†	1405^†
[Ala¹¹,D-Leu¹⁵-Orexin B (2142)	52^‡	0.13^‡

* pK_b value, † K_b value, ‡ EC₅₀ value

References

Smart et al (1999) Cahracterization of recombinant human orexin receptor pharmacology in a Chinese hamster ovary cell line using FLIPR. Br.J.Pharmacol. 128 1. Sutcliffe and de Lecea (2000) The hypocretins: excitatory neuromodulatory peptides for multiple homeostatic systems, including sleep and feeding. J.Neurosci. Res. 62 161. Smart (1999) Orexins: a new family of neuropeptides. Br.J.Anaesth. 83 695. Smart et al (2001) SB-334867-A: the first selective orexin-1 receptor antagonist. Br.J.Pharmacol. 132 1179. Asahi et al (2003) Development of an Orexin-2 receptor selective agonist [Ala¹¹,D-Leu¹⁵orexin -B. Bioorg.Med.Chem.Letts. 13 111. Langmead et al (2004) Characterisation of the binding of [³H]-SB-674042, a novel nonpeptide antagonist, to the human orexin-1 receptor. Br.J.Pharmacol. 141 340.