Alert wakefulness

Berridge C., O Neil J., Wilier K (1999). Amphetamine acts within the medial basal forebrain to initiate and maintain alert waking. Neuroscience 93,... 

Alert Wakefulness. In wakefulness, the EEG shows a high level of low voltage fast (LVF) frequency activity (9-10 Hz a activity mixed with low amplitude ]3 activity). The EMG shows a high level of tonic activity and the EOG shows frequent eye movements. 

Treatment of excessive daytime sleepiness in narcolepsy and other sleep disorders may require the use of sustained- and immediate-release stimulants to effectively promote wakefulness throughout the day and at key times that require alertness. 

It is commonly assumed that the ubiquitous office coffee pot is heavily used by workers in order to increase their levels of wakefulness, alertness, and, more generally, arousal.4 There may, however, be a number of additional perceived or actual benefits of work-related caffeine intake. Headaches, for example, are often reported in work settings, and one study showed that workers sometimes consume caffeine primarily to relieve them.101 This finding is consistent with the widespread medical use of caffeine to treat headache.102103... 

The second constellation of narcoleptic symptoms can be summarized under the rubric of excessive daytime sleepiness, or an inability to regulate wakefulness. As recently reviewed by Mochizuki et al. (2004), at least four explanations have to date been proposed for this sleepiness a deficit in arousal, an impaired circadian alertness signal, abnormal homeostatic regulation of non-REM sleep, and excessive vigilance state fragmentation. These mechanisms are not mutually exclusive, and there are possible roles for orexin signaling in each of them, as we review in the following sections. 

One class of stimulants, the amphetamines, was synthesized originally as possible alternative drugs for the treatment of asthma and was a principal component of the original Benzedrine . Amphetamine-like stimulants are known and consumed especially for their activity-sustaining effects (i.e. increased alertness, strength, and endurance). Their wake-promoting properties... 

Kamimori G. H., Penetar D. M., Headley D. B. et al. (2000). Effect of three caffeine doses on plasma catecholamines and alertness during prolonged wakefulness. Eur. J. Clin. Pharmacol. 56, 537-44. 

Dopamine has an alerting effect. Neurochemicals involved in wakefulness include norepinephrine and acetylcholine in the cortex and histamine and neuropeptides (e.g., substance P and corticotropin-releasing factor) in the hypothalamus. 

The goal of therapy is to maximize alertness during waking hours and improve quality of life (see Fig. 72-1). 

Our family is so informed that I don t have to worry about chemicals in our house. And we eat right and take a lot of vitamins, so even if sometimes I do run into perfume or something, it won t bother me now as much as it would have maybe two years ago. I don t think about it too much, but I m cautious. I m alert every day, and that pretty much keeps me well. But occasionally I get a wake-up call. Sometimes I get rashes or hives, or I ll get an instant sore throat when I m exposed to certain hair products and that kind of thing. I get a migraine about once a month, which jolts me back to the reality that I have to deal with this. Or, if I don t want to ask my friends to not wear perfume, and I just ignore it, I get sick. But I don t dwell on it. 

The final category is termed the sleep-wake schedule disorders. These are seen in people who get their days and nights turned around. The most common examples are shift workers and travelers with jet lag. Additionally, in the elderly, especially those with dementia, a malfunction in the circadian biological rhythm that regulates sleep can leave them awake and alert at night but drowsy and sleeping during the day. 

Eszopiclone has been approved for the treatment of patients who experience difficulty falling asleep, poor sleep maintenance, and for long-term treatment of insomnia. Clinical trials have shown that eszopiclone improved sleep onset, sleep maintenance, total sleep time, sleep quality, and daytime functioning compared with placebo. Improved wake time alertness, concentration, and sense of well-being were reported. Eszopiclone was well tolerated, with only mild adverse events reported. There was no evidence of dmg-drug interactions, tolerance, residual drowsiness or treatment-related rebound insomnia. The recommended dose to improve sleep onset and maintenance is generally between 1 and 3 mg. 

Circadian clock-controlled rhythms provide most organisms with an orchestrated temporal programme that allows for appropriate timing of physiology (i.e. blood pressure, hormonal levels) and behaviour (i.e. alertness, sleep-wake cycle). The mammalian central circadian pacemaker resides in the suprachiasmatic nucleus (SCN) of the brain (Weaver 1998). At the molecular level, the core oscillator driving the mammahan clock consists of interconnected autoregulatory... 

---