Orexin Receptor Data

Receptor Subtype OX1 Receptors OX2 Receptors
G protein Gq/11 Gq/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 Ki 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

* pKb value, † Kb 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.