Sleep extension

Roehrs T, Shore E, Papineau K, Rosenthal L, Roth T. A two-week sleep extension in sleepy normals. Sleep 1996 19(7) 576-582. 

Although large-scale controlled studies on chronic partial sleep deprivation and sleep extension are difficult to execute, we have been able to acquire a great deal of knowledge from the well-conducted investigations that have been carried out to date. Chronic partial sleep deprivation unquestionably leads to accumulation of impairment and progressively increased sleep tendency, the sum of which have been referred to as sleep debt. Once sleep debt has accrued, it can only be paid back by extra sleep. 

Roehrs T, Timms V, Zwyghuizen-Doorenbos A, Roth T. Sleep extension in sleepy and alert normals. Sleep 1989 12 449 157. 

Since 1986, when the very first reports on the use of microwave heating to chemical transformations appeared [147,148], microwave-assisted synthesis has been shown to accelerate most solution-phase chemical reactions [24-27,32,35]. The first application of microwave irradiation for the acceleration of reaction rate of a substrate attached to a solid support (SPPS) was performed in 1992 [36]. Despite the promising results, microwave-assisted soHd-phase synthesis was not pursued following its initial appearance, most probably as a result of the lack of suitable instriunentation. Reproducing reaction conditions was nearly impossible because of the differences between domestic microwave ovens and the difficulties associated with temperature measurement. The technique became a Sleeping Beauty interest awoke almost a decade later with the publication of several microwave-assisted SPOS protocols [37,38,73,139,144]. There has been an extensive... 

Several neurotransmitters and neuropeptides influence sleep-wakefulness, including REM sleep. Although NA-ergic and ACh-ergic influences have been studied more extensively, other neurotransmitters also play an important role in the modulation of REM sleep (Sakai, 1986 Mallick et al, 1999 Jones, 2005). 

Subsequent to the extensive medicinal chemistry exploration of Orexin antagonism, its utility in the treatment of sleep disorders in man has been reported recently. This important milestone for the therapeutic validation of the target results from the 0X1 /OX2 receptor antagonist ACT-078573 (20) [57], SB-649868 has also been announced to be in phase II clinical development, but neither the structural formula nor the results have been reported to date [58,59]. Moreover, insomnia treatments based on orexin modulation may be addressed by not only receptor antagonism but by inhibition of pathways related to the genesis of the bioactive peptides Orexin A or B, e.g. inhibition of Orexin-converting enzyme [60]. 

The alterations in neurotransmitter activity which trigger or accompany the onset of natural sleep and distinguish slow wave or non-REM from REM sleep, provide one of the most compelling arguments in favour of chemical neurotransmission being specifically involved in mechanisms of conscious awareness. For an extensive review on neurochemistry and sleep, see Gottes-man (1999). 

Increasing evidence indicates that patients with DLB experience changes in sleep behaviour and sleep architecture, both of which add to carer burden and may lead to prescription of additional medication. Sleep in DLB has not been as extensively investigated as in AD in which reductions in REM sleep (Ancoli-Israel et ah, 1994) nocturnal wandering and confusion (Ancoli-Israel et ah,... 

In chnical trials, zolpidem shortened sleep latency, improved the quahty of sleep, and accelerated the restoration of normal sleep patterns (Lee, 2004). In insomniac patients it increased the amount of slow wave, restorative sleep as seen in normal sleepers. Zolpidem has high oral bioavailability (70%), a short duration of action (tj /2 = 2 h), and is relatively highly bound to plasma proteins (92%). The recommended dose is generally 10 mg/day as needed. Zolpidem is extensively metabolized, mainly by CYP3A4 but also by CYP1A2 and CYP2C9, and its major metabolites do not appear to have pharmacological activity. It has minimal daytime residual effects, and a low risk for tolerance and abuse. The safety profile showed a low incidence of adverse events, close to that observed with placebo. The medicine is available in over 80 countries. 

Extensive sleep studies have been conducted with a variety of sedative-hypnotic drugs, and all of these drugs appear to alter the normal distribution of rapid eye movement (REM) and non-REM sleep. Most of the older sedative-hypnotic agents markedly depress REM sleep. In contrast, when the benzodiazepines are used in appropriate doses, they depress REM sleep to a much smaller extent. As with treatment of anxiety, the choice... 

There is less therapeutic experience with the newer zaleplon than with zolpidem. Zaleplon has a rapid onset and a half-life of approximately 1 hour. It is extensively metabolized by aldehyde dehydrogenase, so that less than 1% of a dose is excreted unchanged. Because of its rapid onset of action and short biological half-life, zaleplon is well suited for treatment of sleep onset insomnia. Its short half-life often does not ensure a full 8 hours of sleep. 

The purpose of this chapter is to provide an update of research on 1) the sleep laboratory and computerized sleep EEG findings in depression and 2) the effects of antidepressants on sleep efficiency and sleep stages as well as on computerized sleep EEG patterns. Documentation was based on a MEDLINE library search and on references provided in extensive reviews, such as those by C. F. Reynolds and Kupfer (1987), G. W. Vogel et al. (1990), Benca et al. (1992), van Bemmel (1993), M. Berger and Riemann (1993), Armitage (1995), Montero and Berger (1995). 

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