Abstract
BackgroundModafinil is a wake-promoting drug and has been widely used for daytime sleepiness in patients with narcolepsy and other sleep disorders. A recent case series reported that daily oral modafinil alleviated hypercapnic respiratory failure in patients with COPD. However, the precise action of modafinil on respiration such as hypercapnic and/or hypoxic ventilatory responses remains unclear. The aim of this study is to clarify the effect of modafinil on the ventilatory control.MethodsWe investigated the hypothesis that modafinil enhances resting ventilation as well as the stimulatory ventilatory responses to hypercapnia and hypoxia. We addressed the issue by examining minute ventilation, respiratory rate and volume components using plethysmography, combined with a concurrent EEG monitoring of the level of wakefulness before and after administration of modafinil in two doses of 100 mg/kg and 200 mg/kg in unanesthetized mice. In addition, we monitored the effect of the lower dose of modafinil on mice locomotor activity in a freely moving condition by video-recording.ResultsWakefulness, locomotor activity and variability of the breathing pattern in tidal volume were promoted by both doses of modafinil. Neither dose of modafinil increased the absolute values of resting ventilation or promoted the ventilatory responses to hypercapnia and hypoxia. Rather, higher dose of modafinil slightly suppressed respiratory rate in room air condition.ConclusionsModafinil is conducive to the state of wakefulness but does not augment resting ventilation or the hyperventilatory responses to chemical stimuli in unanesthetized rodents.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0466-9) contains supplementary material, which is available to authorized users.
Highlights
Modafinil is a wake-promoting drug and has been widely used for daytime sleepiness in patients with narcolepsy and other sleep disorders
Modafinil is a widely-used wake-promoting drug for treating somnolence in narcolepsy and residual sleepiness persisting in obstructive sleep apnea despite continuous positive airway pressure treatment [1,2,3]
Ventilation and its stimulatory responses to hypercapnia and hypoxia assume a depressive vein in sleep; the condition which modafinil is expected to counteract
Summary
Modafinil is a wake-promoting drug and has been widely used for daytime sleepiness in patients with narcolepsy and other sleep disorders. Ventilation and its stimulatory responses to hypercapnia and hypoxia assume a depressive vein in sleep; the condition which modafinil is expected to counteract. The assumption was strengthened by a recent report demonstrating that modafinil, given orally on a daily basis, alleviated hypercapnic respiratory failure in COPD patients (i.e., improving oxygenation, and lowering the arterial carbon dioxide level) without adverse effects [9]. This off-label use of modafinil opens a new door to regulate hypercapnic respiratory failure in noncompliance patients with non-invasive ventilation [10]. The precise action of modafinil on the respiratory control system has not been fully investigated
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