Effects of Low-Dose Naloxone on Subjective Alertness and Pupil Diameter in Normal and Narcoleptic Subjects

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Abstract
Recent evidence suggests that endogenous opiates may be involved in the pathophysiology of narcolepsy. To test this theory, the effect of 0.8 mg naloxone hydrochloride on pupil size and subjective alertness was measured in normal and narcoleptic subjects. Naloxone resulted in significant pupillary constriction in the normal but not in the narcoleptic subjects. The extent of contraction of the pupil light reflex was reduced significantly in the narcoleptic but not in the normal subjects. There was no effect on subjective ratings of alertness on the Stanford Sleepiness Scale or the visual analogue scale in either group. The naloxone-related miosis in the normal group confirms that naloxone is not a pure opiate antagonist. The lack of naloxone-related miosis in the narcoleptics suggests that narcoleptic individuals do not respond to naloxone as do normal individuals. However, this difference can not be definitely attributed to the antagonism of endogenous opiates. The reduction of the extent of contraction of the light reflex suggests that naloxone caused an increase in supranuclear inhibition of parasympathetic pupil reflex activity. However, this finding may have resulted from mechanical limitations of a small pupil or technical limitations of the recording equipment. This study does not support previous reports that naloxone causes an increase in subjective alertness in narcoleptics.

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