Sleep inducers

Fused isoxazoles (631) were prepared as GABA analogs (75MI41604) and some exhibited CNS depression effects (74JAP(K)7480062) or were effective as minor tranquilizers, muscle relaxants and/or sleep inducers (76USP3966748, 79USP4163057). 

Meparfyiiol, a mild hypnotic or sleep-inducing agent... 

Porrka-Hei.skanen, T, et al., 1997. Adeno.sine A mediator of die. sleep-inducing effects of prolonged wake-fnlne.ss. Science 276 1265-1268. 

C04-0068. Phenobarbital is a sleep-inducing dmg whose chemical formula is C12 H12 N2 O3. It is... 

Satoh, S., Matsumura, H., Suzuki, F., Hayaishi, O. (1966). Promotion of sleep mediated by the A2a adenosine receptor and possible involvement of this receptor in the sleep induced by prostaglandin D2 in rats. Proc. Natl Acad. Sci. USA 93, 5980-4. 

Porkka-Heiskanen, T., Strecker, R. E., Thakkar, M. el al (1997). Adenosine a mediator of the sleep-inducing effects of prolonged wakefulness. Science 276, 1265-8. 

Figure 3.1 Schematic representation of communication between pontine cholinergic REM-ON, NA-ergic REM-OFF and GABA-ergic neurons in the brainstem and influence of brainstem wake- and sleep-inducing areas on REM-ON and REM-OFF neurons for the regulation of REM sleep. Refer to the text for details. The abbreviations are same as in the text (+) indicates excitation and (—) indicates inhibition.

Sallanon, M., Sakai, K., Buda, C., Puymartin, M. Jouvet, M. (1988). Increase of paradoxical sleep induced by microinjections of ibotenic acid into the ventrolateral part of the posterior hypothalamus in the cat. Arch. ltal. Biol. 126, 87-97. 

A significant decrease in wakefulness with a concomitant increase in NREM sleep was also seen with systemic (20 mg/kg) or local application of a-FMH (50 pg in 1 pi) in the TMN region of cats. Although the sleep-inducing effect of a-FMH began 8 h after systemic administration and lasted for one day (Lin et at, 1988), the sleep-inducing effect appeared within 2 h of local application and its most prominent effect lasted for 9 h. In contrast, local microinjections of SKF-91488 (50 pg in 1 pi), a specific inhibitor of the catabolic enzyme HMT, produced an immediate increase in wakefulness, with a concomitant decrease in NREM and REM sleep that lasted for 6 h (Lin et at, 1986). 

Although systemic administration of thioperamide in rats induced a dose-dependent increase in wakefulness with a concomitant reduction in NREM and REM sleep, systemic administration of (R)a-methylhistamine had no effect (Monti et al., 1991). In contrast, bilateral application of (R)a-methylhistamine into the TMN region of rats increased NREM sleep with a concomitant decrease in wakefulness and REM sleep. The NREM-sleep-inducing effect of (R)a-methylhistamine was attenuated if the rats were pretreated with thioperamide (4.0 mg/kg) (Monti et al, 1991). 

Oral administration of the H3 receptor agonist BP 2.94 (20-30 mg/kg) to rats produced a dose-dependent increase in NREM sleep without a significant change in wakefulness or REM sleep. With the highest dose of BP 2.94 (30 mg/kg), the increase in NREM sleep was observed during the second hour and the effect lasted for 6 h. Pretreatment with the H3 receptor antagonist carboperamide (30 mg/kg) prevented the sleep-inducing effects of BP 2.94. In contrast, oral administration of carboperamide (20-30 mg/kg) produced a dose-dependent increase in wakefulness with a concomitant decrease in NREM and REM sleep (Monti et al., 1996). 

Friedman, A. H. 8r Walker, C. A. (1969). Rat brain amines, blood histamine and glucose levels in relationship to circadian changes in sleep induced by pentobarbitone sodium. J. Physiol. 202, 133-46. 

Zhdanova, I. V., Wurtman, R. J., Lynch, H. J. et al. (1995). Sleep-inducing effects of low doses of melatonin ingested in the evening. Clin. Pharmacol. Ther. 57, 552-8. 

Jouvet, M. (1984a). Indolamines and sleep-inducing factors. In Sleep Mechanisms, ed. A. Borbely J.-L. Valatx, pp. 81-94. Berlin Springer-Verlag. 

Onoe, H., et al. (1988). Prostaglandin D2, a cerebral sleep-inducing substance in monkeys. Proc. Natl. Acad. Sci. USA 85, 4082-6. 

The sleep-inducing effect of some antidepressants has been used as an additive strategy in depressed patients with complaints of insomnia to negate the side effects of BZDs that could be confused with worsening depressive symptoms, including asthenia, diurnal sedation, and concentration and memory problems. 

Some CNS stimulants have an effect on the same systems that are involved in wakefulness, including glutamate-, NE-, DA-, 5-HT-, histamine-, hypocretin- and ACh-containing neurons. This group includes molecules such as cocaine, amphetamine, and nicotine. The sleep-promoting systems are concentrated in the medial part of the brainstem, dorsal reticular substance of the medulla, anterior hypothalamus, and basal forebrain (Jones 2005). Other stimulants, such as caffeine and theophylline, block some sleep-inducing mechanisms. Modafinil is also a CNS stimulant with an unknown mechanism of action. 

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