The present and future of synthetic orexin receptor agonists
Related Experiment Video
Updated: Jul 24, 2025
Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography
Published on: September 20, 2016
Tsuyoshi Saitoh1, Takeshi Sakurai1
1Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan; International Institute for Integrative Sleep Medicine (IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Abstract:
The neuropeptide orexin/hypocretin plays a crucial role in various physiological processes, including the regulation of sleep/wakefulness, appetite, emotion and the reward system. Dysregulation of orexin signaling has been implicated in hypersomnia, especially in narcolepsy, which is a chronic neurological disorder characterized by excessive daytime sleepiness (EDS), sudden loss of muscle tone while awake (cataplexy), sleep paralysis, and hallucinations. Small-molecule orexin receptor agonists have emerged as promising therapeutics for these disorders, and significant progress has been made in this field in the past decade. This review summarizes recent advances in the design and synthesis of orexin receptor agonists, with a focus on peptidic and small-molecule OX2R-selective, dual, and OX1R-selective agonists. The review discusses the key structural features and pharmacological properties of these agonists, as well as their potential therapeutic applications.
Related Concept Videos
01:25Drug-Receptor Interaction: Agonist
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...
01:22Opioid Receptors: Overview
01:17Sedatives and Hypnotics Drugs: Miscellaneous Agents
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
01:15Opioid Analgesics: Synthetic and Semisynthetic Opioids
01:25Adrenergic Agonists: Indirect-Acting Agents
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
01:16Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...