Orexin Receptor Agonists
Orexins are a group of neuropeptides discovered in 1998 that regulate the sleep-wake cycle and are described to modulate the metabolic energy balance as well as reward and addiction behaviour. Orexins exert their physiologic effects by two G protein-coupled receptors (GPCR), the orexin receptor (OxR) 1 and 2. Both, orexins and their receptors, are mainly expressed in specialized neurons in the brain, but were also found in the body periphery.
Given that deregulations of our sleep architecture affect roughly 20-30% of all citizens in the western industry nations, the orexin receptor system as a key player in regulating the arousal and wakefulness became a highly interesting pharmacological target. Thereby, OntoChem focusses on the development of molecules that activate the signalling of orexin receptors, so called orexin receptor agonists. Such compounds are potential pharmacological candidates for the treatment of narcolepsy, a disease that is characterized by a completely deregulated sleep-wake rhythm and excessive daytime sleep attacks.
Functional characterization of the action of orexins in different CNS tissue models