New approaches for the treatment of sleep disorders.

Epidemiological studies have established that sleep disorders are common and often untreated. Besides having a negative impact on overall health, these conditions can significantly disrupt normal daily functions. While a number of drugs are employed in the treatment of sleep disorders, safety, tolerability, and variable efficacy limit their utility. Clinical developments in the area have been facilitated especially by advances in neurobiology and neuropharmacology. In this regard, a wide array of neuroactive substances has been found to be responsible for regulating sleep and wakefulness. Advances in the understanding of neurotransmitter and hormone receptor mechanisms and classifications have led to new opportunities for developing novel therapeutics for treating sleep disorders. Provided in this report is an overview of some of the more prevalent sleep disorders, including narcolepsy, insomnia, obstructive sleep apnea syndrome, and restless legs syndrome, with a summary and critique of medications used to treat these conditions. For each disorder, information is provided on recent approaches taken to develop novel therapeutics based on laboratory findings relating to the underlying biological abnormalities associated with the condition, in addition to approaches that leverage existing therapeutics to develop new treatment options for patients. Significant advances in the future await a better understanding of the underlying pathophysiology of these conditions and of the neurobiological alterations associated with these disorders. It is hoped that some of the research directions described herein will stimulate additional research in this area and thereby help foster the discovery of novel agents for treating major sleep disorders.