Obstructive sleep apnea: The potential for serotonergic pharmacotherapies

Abstract

Obstructive sleep apnea syndrome is a highly prevalent disorder, associated with numerous cardiovascular and neurobehavioral morbidities. A unique feature of this syndrome is the sleep-state dependency of upper airway collapse and obstruction. Indeed, individuals with obstructive sleep apnea have normal breathing while awake and only manifest airway obstruction in sleep. This sleep-state dependency for obstruction strongly supports the concept that drugs targeting the neurochemical events that underlie the state-dependent obstruction should effectively treat obstructive sleep apnea. Tremendous progress has been made in understanding the neurochemical mechanisms involved in state-dependent control of breathing. It is apparent from this work that there are many potential avenues for pharmacotherapies, including several promising directions for serotonergic therapies. This chapter provides an update on the involvement of serotonin in breathing and in apneas, and then summarizes trials of serotonergic agonists and antagonists in animal models and humans with obstructive sleep apnea. Future directions are suggested for successful development of safe and effective serotonergic pharmacotherapies for obstructive sleep apnea. © 2008 Birkhäuser Verlag AG.