naloxone and Narcolepsy

The effect of Naloxone (0.4 mg i.v.) was studied in 10 patients suffering from narcolepsy. The diurnal polysomnographic recordings showed that Naloxone leads to an increase in the latency of REM sleep (P less than 0.05), to a shortening of its total duration and to a decrease in the average amount of phasic manifestations in 1 min. of REM sleep (P less than 0.05). The Polygraphic sleepiness score for REM sleep decreased significantly (P less than 0.01). Naloxone led also to the disappearance of stages 3 and 4 NREM sleep, and to an increase in the total duration of stage 1 NREM sleep. Naloxone caused no change in the total performance in Bourdon's test; though it did enhance attention. There were no changes in the subjective perception of the state of arousal or of the psychomotor tempo. It was found no post-Naloxone alterations of blood pressure, body temperature, pulse or pupillary diameter. The above findings support the hypothesis that an hyperactive endorphinergic system participates in the pathophysiology of narcolepsy.

Topics: Adult; Female; Humans; Male; Middle Aged; Naloxone; Narcolepsy; Sleep Stages

Narcolepsy has been defined as a disorder of excessive sleep often associated with cataplexy, sleep paralysis and hypnagogic hallucinations. Although the pathophysiology of the narcoleptic syndrome is not well understood, derangement in the functions of CNS catecholamines and serotonin (5-HT) have been implicated. In the present paper we summarize evidence to suggest a role for the endogenous opioids in the regulation of normal sleep and in the pathophysiology of the narcoleptic syndrome.

Topics: Humans; Morphine; Naloxone; Narcolepsy; Neurotransmitter Agents; Sleep; Sleep, REM

Currently the most prevailing hypothesis attempting to explain the pathophysiology of Tourette's syndrome (TS) suggests that the disease results from dopaminergic (DA) hyperactivity (Golden, 1986). Evidence for this hypothesis is indirect and includes the favorable response of these patients to haloperidol, exacerbation of symptoms with dopaminergic drugs (e.g., methylphenidate) and the findings of reduced DA metabolites in the CSF of some TS patients (Singer et al., 1982). We have recently suggested that deranged opioid functions may also be important in the pathophysiology of TS (Sandyk, 1985). Our hypothesis was based on the favorable response of a subgroup of patients to administration of opiate antagonists (e.g., naloxone, naltrexone) (Sandyk et al., 1986), and is also supported by a recent finding demonstrating depletion of striatal dynorphins in a subject with TS (Haber et al., 1986). Furthermore, based on several clinical features of the disease, we have recently suggested that the hypothalamus could be a site of dysfunction in the disease (Sandyk et al., 1986). To investigate the possible role of deranged opioid-mediated hypothalamic functions in TS further, we tested the effects of acute naloxone (Nx) challenge on plasma FSH and LH levels in 5 male TS patients (aged 11-16 years) and in 4 non-TS-diseased controls (narcoleptics). The plasma FSH and LH levels were drawn prior to and 30 min following the intramuscular administration of 1.2 mg of naloxone.

Topics: Adolescent; Child; Endorphins; Follicle Stimulating Hormone; Gonadotropins; Humans; Luteinizing Hormone; Male; Naloxone; Narcolepsy; Tourette Syndrome

Topics: Adult; Attention; Electrophysiology; Female; Humans; Male; Naloxone; Narcolepsy; Psychomotor Performance; Sleep

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.

Topics: Adult; Arousal; Endorphins; Humans; Middle Aged; Naloxone; Narcolepsy; Pupil

Topics: Adult; Humans; Male; Naloxone; Narcolepsy

Topics: Adult; beta-Endorphin; Double-Blind Method; Endorphins; Humans; Male; Middle Aged; Naloxone; Narcolepsy