From past to future: 50 years of pharmacological interventions to treat narcolepsy.

ABSTRACT

The history of narcolepsy research began with the pioneering work of Jean-Baptiste-Édouard Gélineau in the late 19th century. In the 1880s, Gélineau introduced the term "narcolepsy" to describe a condition characterized by sudden and uncontrollable episodes of sleep. His clinical descriptions laid the foundation for our understanding of this complex disorder. Over the last half-century, the pharmacological landscape for narcolepsy treatment has evolved remarkably, shifting from merely managing symptoms to increasingly targeting its underlying pathophysiology. By the 1930s, treatments such as ephedrine and amphetamine were introduced to alleviate excessive daytime sleepiness, marking significant advancements in narcolepsy management. These stimulants provided temporary relief, helping patients maintain wakefulness during the day. As research progressed, the focus shifted towards understanding the disorder's underlying mechanisms. The discovery of orexin (also known as hypocretin) in the late 1990s revolutionized the field. This breakthrough underscored the importance of orexin in regulating sleep-wake cycles and provided new targets for pharmacological intervention. Looking ahead, the future of narcolepsy pharmacotherapy is poised for further innovation. The ongoing exploration of orexin receptor agonists and the potential development of neuroprotective therapeutic targets underscore a promising horizon. Emerging research into the genetic and immunological underpinnings of narcolepsy opens new avenues for personalized medicine approaches and the identification of biomarkers for more precise treatment strategies. Additionally, the refinement of existing treatments through improved delivery systems and the investigation of combination therapies offer opportunities for enhanced efficacy and improved quality of life for patients with narcolepsy.