Dreaming of Better Treatments: Advances in Drug Development for Sleep Medicine and Chronotherapy.

The development of sleep medicines has evolved from ancient herbal sedatives to modern synthetic drugs, driven by deeper understanding of sleep mechanisms. Barbiturates and bromides in the 19th century gave way to benzodiazepines, which promote gamma-amino butyric acid release to inhibit brain signaling. Newer therapies more specifically target the wake-inducing neurotransmitter orexin, reducing side effects. Kinases are predicted to be the next targets for breakthroughs in sleep medicine. Sleep disruptions contribute to the buildup of pathological neuronal proteins in neurodegenerative disorders, so sleep medicine could improve prognosis in such conditions, but medicines that do not fully mimic sleep might worsen disease progression.

Study at a glance

Abstract

Throughout history, the development of new sleep medicines has been driven by progress in our understanding of the mechanisms underlying sleep. Ancient civilisations used their understanding of the sedative nature of natural herbs and compounds to induce sleep. The discovery of barbiturates and bromides heralded a new era of synthetic sleep medicine in the 19th century. This was followed by the development of benzodiazepines that were used to inhibit signalling throughout the brain by promoting gamma-amino butyric acid release and thereby produce loss of consciousness. As our understanding of sleep has deepened, newer therapies have more specifically targeted the wake-inducing neurotransmitter orexin with fewer side effects. Given the newly highlighted role of kinases in sleep/wake regulation, we predict that the next breakthroughs in sleep medicine will likely target these kinases. Given the fundamental role that sleep plays in maintaining brain health through processes such as glymphatic clearance, sleep medicine has therapeutic potential beyond just sleep. Recent evidence suggests that sleep disruptions directly contribute to the build-up of pathological neuronal proteins in neurodegenerative disorders. Therefore, sleep medicine could improve prognosis in disorders such as these. Great attention must be paid to the mechanism of action of each sleep medicine, however, as sleep medicines which do not fully mimic sleep could actually worsen disease progression.