Orexin receptor 2 agonists: a pathophysiologic approach to narcolepsy type 1

Sleep is an essential physiological process vital to maintaining overall well-being. The reticular activating system (RAS), a network of neurons in the brainstem, regulates wakefulness and sleep. While it may seem passive, sleep consists of distinct cycles, each with its unique characteristics and functions. Two key sleep phases are non-rapid eye movement (NREM) and  rapid eye movement (REM).
NREM Sleep
NREM sleep comprises four progressive stages that seamlessly merge:

Narcolepsy is a chronic sleep disorder characterized by pervasive, uncontrolled sleepiness and other sleep disturbances. One of its hallmark symptoms is an abrupt transition to REM sleep upon falling asleep, which causes symptoms typically associated with this phase to occur unexpectedly during wakefulness. These include the following symptoms, which typically last from a minute or two to half an hour.

The sleep cycle, an integral part of human health, consists of several stages with distinct characteristics and functions. It begins with a transition from wakefulness to sleep, known as the light sleep phase, followed by the restorative deep sleep phase, essential for physical recovery and growth. The cycle concludes with the Rapid Eye Movement (REM) phase, characterized by high brain activity and vivid dreaming. Insomnia, a prevalent sleep disorder, involves difficulty falling asleep, staying...

Sedatives and hypnotics encompass a wide range of substances, each with its unique mechanism of action, uses, and potential adverse effects.
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...

Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...

Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...