Hypnotic Activity of Melatonin

Abstract

INTRODUCTION THERE IS MUCH INTEREST CONCERNING THEACTIVITY OF MELATONIN and how melatonin may be used to alleviate disturbances of circadian rhythmicity and insomnia. Experimental work on the possible adjustment of the circadian clock by melatonin is complicated by its sedative activity. This latter effect may improve sleep, thus alleviating the symptomatology of circadian desynchrony, and even normalizing the sleep-wake cycle. Whether melatonin can induce a phase shift of circadian rhythms is an issue much debated. 1,2,3 It may elicit a relatively weak phase shifting effect, but Cziesler 4 has emphasised that this may be insufficient to induce a reliable entrainment. Any such effect with melatonin needs to be established by physiological parameters other than sleep and wakefulness.Although sedative activity of melatonin has been demonstrated, its usefulness as a hypnotic is not clear. Indeed, Roth and Richardson 5 have emphasized that the majority of studies have evaluated only a single dose, or a limited dose range, and that there is a need for unambiguous information on its activity related to dose and to time of administration. Further, dose response data using electroencephalography are essential to an adequate understanding of its activity. Daytime ingestion of melatonin would appear to lead to reductions in sleep latencies, 6,7,8,9 but studies on its activity around the normal time of sleep have failed to establish a useful clinical effect, except possibly in elderly insomniacs. 10,11,12 However, the usefulness of a hypnotic in the management of sleep disturbance associated with shiftwork or with world wide travel would be dependent on it being effective at all times of the circadian cycle, and it is in this context that we have carried out a dose response study on the activity of melatonin when given in the early and late evening in healthy volunteers. The activity of melatonin was studied on nocturnal sleep (23:00-07:30) and on evening sleep (18:00-24:00), using electroencephalography, and was compared with that of a benzodiazepine (temazepam 20 mg) which is often used by individuals coping with irregular patterns of rest in critical situations. METHODS SubjectsThe subjects were healthy male volunteers free of the use of medication. They gave informed consent to take part

Randomised clinical trial of the effects of prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during sleep in healthy people

“…Sleep scheduled outside the phase of nocturnal melatonin secretion is disrupted and characterised by delayed sleep initiation and reduced sleep consolidation, and this can be alleviated by exogenous melatonin administration, and several studies have demonstrated this in healthy individuals (Rajaratnam et al, 2004;Stone et al, 2000;Wyatt et al, 2006). The effects of melatonin are thought to be mediated primarily by MT1 and MT2 receptors, which have a high density in the suprachiasmatic nucleus of the hypothalamus, amongst other areas (Arendt and Rajaratnam, 2008;Srinivasan et al, 2009).…”

The Sleep-Promoting and Hypothermic Effects of Glycine are Mediated by NMDA Receptors in the Suprachiasmatic Nucleus

“…Some hypnotics, such as benzodiazepines, zolpidem, and ramelteon, induce hypothermia within a physiological range (Elliot and White, 2001;Markwald et al, 2010). In some human studies, exogenous melatonin has been shown to induce sleep and lower Tb (Lavie, 1997;Stone et al, 2000;Zhdanova et al, 1995). Similarly, glycine administration before bedtime decreases Tb in human subjects (Nagao et al, 2007).…”

Effects of prolonged‐release melatonin, zolpidem, and their combination on psychomotor functions, memory recall, and driving skills in healthy middle aged and elderly volunteers

“…Several studies reported alterations of alertness and performances by acute melatonin when administered during daytime (Atkinson et al, 2005;Cajochen et al, 1996;Dollins et al, 1993;Graw et al, 2001;Lieberman et al, 1984;Neville and McNaughton, 1986;Rogers et al, 1998) but not when administered during late afternoon or at bedtime in young and middle-aged (20-57 years) healthy volunteers (Paul et al, 2003;Stone et al, 2000;Suhner et al, 1998;Wynn and Arendt, 1988). Furthermore, melatonin administered nightly for 4 weeks improved certain aspects of cognition in healthy elderly subjects (Peck et al, 2004).…”