The effects of transdermal scopolamine on autonomic nervous activity during sleep

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Abstract
We studied the effect of transdermally applied scopolamine (scopolamine-TTS) on autonomic nervous activity during sleep. The double-blind, randomized, crossover study was carried out in six healthy male volunteers by applying 1.5 mg scopolamine-TTS or placebo patch on the retroauricular skin and by monitoring heart rate, cardiac ballistogram, respiration and body movements by using electrocardiogram and static charge sensitive bed. Scopolamine did not decrease the time the subjects desired to sleep (516 min after TTS, 511 min after placebo) or the number of body movements of 3–5 s duration the subjects spontaneously performed during sleep (47 after TTS, 58 after placebo). No adverse effects of scopolamine were reported spontaneously. Scopolamine-TTS slowed the mean heart rate during quiet sleep from 53.2 to 44.9 beats · min−1, and increased the duration of bradycardia in response to body movements (MIB-reflex) from 12.5 to 14.7 s with a significant difference between scopolamine and placebo effects. The bradycardias were not associated with disturbances in cardiorespiratory or central nervous system functions. The cardiac vagomimetic action of scopolamine-TTS could be explained by low plasma drug concentrations (175 pg/ml) primarily blocking only neuronal inhibitory prejunctional muscarinic receptors which regulate acetylcholine release from the autonomic ganglia and parasympathetic nerve-endings. Because of the central role of acetylcholine in the physiological regulation of sleep, the effect of scopolamine-TTS on sleep merits further investigations.