Current Topics in Medicinal Chemistry - Volume 8, Issue 11, 2008

As one of the most obvious and fundamental processes in biology, sleep has attracted a great deal of attention from ancient philosophers to present-day biomedical researchers. Given its importance to normal daily functioning, research into medicinal agents that affect sleep and wakefulness has progressed beyond the empirical exploration of herbal preparations practiced for millennia. When chemists gained the Read More

The fundamental purpose of sleep remains one of the most compelling questions yet to be answered in the area of neuroscience, if not all of biology. A pervasive behavior among members of the animal kingdom, the functional necessity of engaging regularly in sleep is best demonstrated by showing that failing to do so leads to a broad repertoire of pathological outcomes including cognitive, immunological, hormonal, and Read More

Melatonin (N-acetyl-5-methoxytryptamine) is synthesized and released by the pineal gland following a circadian rhythm characterized by high levels during the night. It shows several pharmacological effects on diverse cellular and animal models, mainly related to either its antioxidant activity or to its ability to activate specific receptors (MTr). Melatonin is widely used as a self-administered food additive, but its therapeutic potenti Read More

Nearly one half of the adult population in the U.S. experience some symptoms of insomnia (difficulties with getting to sleep, maintaining sleep, and/or sleep quality) on a weekly basis. Although most people with insomnia complain primarily of issues related to sleep maintenance and quality, current therapeutic approaches, including GABAA agonists, off label antidepressant use, H1 antagonists and melatonin agonists, primaril Read More

Actelion Pharmaceuticals achieved clinical proof-of-concept for the treatment of insomnia in 2007 with the release of Phase II data on Almorexant, a potent dual (OX1R/OX2R) orexin receptor antagonist. GlaxoSmithKline also released clinical efficacy data on an orexin receptor antagonist in 2007 for the treatment of insomnia. With these exciting findings, the search for orexin (or hypocretin) receptor antagonists for the treatment Read More

The histamine H3 receptor is a pre-synaptic auto- and hetero-receptor that controls the release of histamine and a variety of other neurotransmitters in the brain. As such, modulation of the histamine H3 receptor is expected to affect wake via control of the release of histamine and to affect cognition via regulation of several other neurotransmitters including acetylcholine and norepinephrine. Over the last sever Read More

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