Sleep switch

Saper, C. B., Chou, T. C., Scammel, T. E. (2001). The sleep switch hypothalamic control of sleep and wakefulness. Trends Neurosci. 24, 726-31. 

The principal OTC pharmaceutical products include cold remedies, vitamins and mineral preparations, antacids, analgesics, topical antibiotics, antiftingals and antiseptics, and laxatives. Others include suntan products, ophthalmic solutions, hemorrhoidal products, sleep aids, and dermatological products for treatment of acne, dandmff, insect parasites, bums, dry skin, warts, and foot care products (11). More recent prescription-to-OTC switches have included hydrocortisone, antihistamine and decongestant products, antiftingal agents, and, as of 1995, several histamine H2-receptor antagonists. 

Technical term for properties of electrical or neural circuits (flip-flop switch) to rest in two distinct states while avoiding intermediate states (e.g., behavioral state sleep-wake transitions). 

Some arousal-related neurotransmitters, including noradrenaline, serotonin, and acetylcholine, feed back to inhibit POA sleep-active neurons. This aspect of the system has been reviewed previously (McGinty Szymusiak, 2000 Saper et al., 2001). Therefore, once sleep-active neurons are activated, arousal-related neurons are inhibited, and inhibitory control of sleep-active neurons by arousal systems is reduced. In this way, sleep onset is facilitated. That is, the mutually inhibitory systems can switch more quickly from wake to sleep, and back. These mutually inhibitory interactions also promote stability of both waking and sleep. 

McGinty, D. Szymusiak, R. (2000). The sleep-wake switch a neuronal alarm clock. 

Figure 2.4 Flip-flop switch model of wake and slow wave sleep active systems. Mutually inhibitory connections exist between GABAergic/Galaninergic slow wave sleep active neurons in the ventrolateral preoptic area (VLPO) of the anterior hypothalamus and aminergic neurons in the hypothalamus (histamine (HA) neurons in the tuberomammillary nucleus (TMN)) and brainstem (serotonin (5-HT) neurons in the dorsal raphe (DR) and noradrenaline (NA) neurons in the locus coeruleus (LC)). Orexinergic neurons in the perifornical hypothalamus (PFH) stabilize the waking state via excitation of the waking side of the flip-flop switch (aminergic neurons).

The flip-flop switch controlling wake-sleep transitions... 

Electrophysiologic and behavioral observations in LSD-treated animals may give some hint as to the switch in attentiveness in the presence of a moderately high state of arousal, which is characteristic of LSD in man. One would expect further clarification of the physiologic role of the raphe with respect to REM sleep because, in nature, this is one state in which a natural shift to primary process thinking and plastic and sensory thought and perceptual processes (with a compelling sense of conviction) can occur. 

Pemoline is a less potent stimulant than methylphenidate or dextroamphetamine. It should be initiated at 18.75 mg taken each morning with breakfast and can be increased in increments of 18.75mg every week or so. Typical dosing for pemoline ranges from 60 to 200mg/day in treating narcolepsy. Because pemoline is less potent than other stimulants, it is more likely to be ineffective, even at its higher doses. When pemoline does not relieve daytime sleepiness or sleep attacks, then the patient should be switched to a different stimulant. 

Should the first medication fail to provide satisfactory relief from the drowsiness and sleep attacks of narcolepsy, the patient should be switched to an alternative... 

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