Contents



Preface

The pineal hormone of "darkness," melatonin (*N*-acetyl-5-methoxytryptamine), is biosynthesized and secreted mainly at night. It is an important component in the regulation of seasonal and circadian rhythms. Its action is believed to be mediated through a family of specific, high-affinity, G-protein-coupled cell membrane receptors. It is ubiquitous throughout both the animal and plant kingdoms and must have a long evolutionary history as a hormone. The secretion of the hormone is closely synchronized with the habitual hours of sleep in humans. Ingestion of melatonin affects sleep propensity as well as duration and quality of sleep. Sleep problems become more common in the elderly in whom there is also a loss in the

Melatonin treatment has therapeutic value in some blind subjects, restoring their disturbed circadian rhythm. It also has potential in the treatment of seasonal affective disorder (SAD), which afflicts some people during the short winter days, and it has been used to reset the clock in sufferers from jet lag. Melatonin has been implicated in a range of other conditions, including Parkinson's disease, Alzheimer's and other neurodegenerative conditions, and in certain cancers. It has also recently been shown that melatonin can be synthesized by mammalian skin, where it may be

Several synthetic molecules have shown interesting melatoninergic activity, frequently greater and more selective than that of the endogenous hormone. Ramelteon was the first prescription medication for insomnia, and the only hypnotic indicated for longterm treatment of insomnia as it does not have hangover, addictive, or withdrawal effects. Another melatonin analogue, agomelatine, has recently been introduced as an

The use of melatonin as a drug is hampered by its short biological half-life and poor bioavailability. As a result, dosage forms, which mimic the physiologically secreted

The eight chapters in this book deal with all these aspects. The initial chapter provides an account of most of the synthetic melatoninergic agents available thus far, and is addressed to a wide non-cognizant readership. Briefly, this chapter focuses on the synthetic routes towards synthetic melatonin derivatives, first of their aromatic nucleus, then of the functionalities that have been introduced to the nucleus, and finally those analogues with restrained conformations and those that are optically active. The second chapter is pivotal to the research on melatonin's direct involvement with sleep and the dysfunctions caused by insomnia, which are also presented in the third chapter. Moreover, in the latter chapter, the use of synthetic melatonin, as a food supplement in various dosage forms such as pills, granules for oral solution, orodispersable granules, and syrups in order to address patients' needs, is described. The fourth chapter focuses on the electrophysiological and the antiarrhythmic properties of melatonin. The acute and chronic protective mechanisms of melatonin are analyzed with an emphasis on transmembrane potentials and intercellular communication. An outstanding antifibrilatory effect

important in regulating hair growth and pigmentation physiology.

antidepressant and appears to have few side effects.

melatonin concentration versus time model, are limited.

production of melatonin.
