SB-668875 is a novel, selective peptide agonist at OX2 orexin receptors. SB-668875 possesses advantages over Orexins A and B which are equipotent at OX2 orexin receptors. The orexins can cause direct and reversible depolarisation of the postsynaptic membrane. The rank order of potencies of orexin receptor agonists to excite serotonergic DRN neurones is orexin-A = orexin-B > SB-668875-DM. In contrast, the rank order of potency of these agonists to excite noradrenergic locus coreleus (LC) neurones is orexin-A > orexin-B > SB-668875-DM.
