Contents

#### **Preface XI**


Chapter 6 **Melatonin in Childhood Epilepsy and in Child Neurology 123** Justyna Paprocka, Marek Kijonka and Maria Sokół

Chapter 7 **Measurement of Plasma Tryptophan Metabolites: Clinical and Experimental Application for Depression and Stress States Assessment 143** Akikazu Takada, Fumiko Shimizu and Junichi Masuda Chapter 8 **Salivary Melatonin at Night: Responding to the Night Lighting and Cow's Milk Consumption at Breakfast in Japanese Junior High and University Students 161** Hitomi Takeuchi and Tetsuo Harada

Preface

in different disorders.

peutically delivered.

Melatonin, the pineal neurohormone, also produced by various other tissues and cells, is a pleiotropic molecule acting in the center of the integrative molecular mechanisms of the or‐ ganism, based on interlinkages of the regulatory systems: neural, endocrine, immune, and

Its substantial physiological and pathological implications, from outstanding antioxidant ca‐ pacity, circadian integration, and internal clock modulation, to its intimate relation to vari‐ ous diseases, the control of sleep, the metabolic syndrome, weight control, diabetes and insulin resistance, mitochondrial effects, cardiovascular decompensation, neurodegenera‐ tion, inflammatory diseases, and, most of all, aging, prove an exceptional multiplicity of ac‐

This book is unique in covering the most important topics related to melatonin and its in‐ dole derivatives, from synthesis in the pineal gland and subsequent tissues and cells, to re‐ ceptors characterization and catabolic pathways, all aspects of molecular biochemistry used to understand the multiple actions of melatonin. Other important topics include pharmaco‐ logical aspects implied by specific receptors binding and biological effects proven at the cel‐ lular level, from antioxidant cascade activation to metabolic enzymes and signal factors modulation, detailing the pathological implications of melatonin and tryptophan depletion

The therapeutic uses of melatonin formulations imply a particular pattern, and are subject of intense research due to its solubility profile and bioavailability characteristics. A consequent chapter is extensively dedicated to this important feature, highlighting the importance of

All in all, this book provides a systematic and updated overview of melatonin biochemical mechanisms of action, pharmacological features, and clinical uses, clutching the subject with complete details of pharmaceutical formulations designed for different routes of administra‐ tion and different health issues, aiming at optimal melatonin bioavailability when thera‐

We highly acknowledged the interest and raised professional profile of all authors who have contributed to writing this book, and the academic and scientific support provided by Alina Crenguța Nicolae, PhD, who assisted our work during in whole period of the project.

**Cristina Manuela Drăgoi and Alina Crenguța Nicolae**

"Carol Davila" University of Medicine and Pharmacy

Faculty of Pharmacy

Bucharest, Romania

tions, distinguishing melatonin from many other important signal molecules.

genetic, all embodying the uniqueness of human architecture.

intensively controlled release formulations in melatonin therapy.


Marilena Vlachou and Angeliki Siamidi

## Preface

Chapter 7 **Measurement of Plasma Tryptophan Metabolites: Clinical and**

Akikazu Takada, Fumiko Shimizu and Junichi Masuda

Chapter 8 **Salivary Melatonin at Night: Responding to the Night Lighting**

**Section 3 Pharmaceutical Formulations for Enhancing Melatonin's**

Chapter 9 **Melatonin Modified Release Formulations Designed for Sleep**

**High and University Students 161** Hitomi Takeuchi and Tetsuo Harada

Marilena Vlachou and Angeliki Siamidi

**Assessment 143**

**VI** Contents

**Bioavailability 183**

**Disorders 185**

**Experimental Application for Depression and Stress States**

**and Cow's Milk Consumption at Breakfast in Japanese Junior**

Melatonin, the pineal neurohormone, also produced by various other tissues and cells, is a pleiotropic molecule acting in the center of the integrative molecular mechanisms of the or‐ ganism, based on interlinkages of the regulatory systems: neural, endocrine, immune, and genetic, all embodying the uniqueness of human architecture.

Its substantial physiological and pathological implications, from outstanding antioxidant ca‐ pacity, circadian integration, and internal clock modulation, to its intimate relation to vari‐ ous diseases, the control of sleep, the metabolic syndrome, weight control, diabetes and insulin resistance, mitochondrial effects, cardiovascular decompensation, neurodegenera‐ tion, inflammatory diseases, and, most of all, aging, prove an exceptional multiplicity of ac‐ tions, distinguishing melatonin from many other important signal molecules.

This book is unique in covering the most important topics related to melatonin and its in‐ dole derivatives, from synthesis in the pineal gland and subsequent tissues and cells, to re‐ ceptors characterization and catabolic pathways, all aspects of molecular biochemistry used to understand the multiple actions of melatonin. Other important topics include pharmaco‐ logical aspects implied by specific receptors binding and biological effects proven at the cel‐ lular level, from antioxidant cascade activation to metabolic enzymes and signal factors modulation, detailing the pathological implications of melatonin and tryptophan depletion in different disorders.

The therapeutic uses of melatonin formulations imply a particular pattern, and are subject of intense research due to its solubility profile and bioavailability characteristics. A consequent chapter is extensively dedicated to this important feature, highlighting the importance of intensively controlled release formulations in melatonin therapy.

All in all, this book provides a systematic and updated overview of melatonin biochemical mechanisms of action, pharmacological features, and clinical uses, clutching the subject with complete details of pharmaceutical formulations designed for different routes of administra‐ tion and different health issues, aiming at optimal melatonin bioavailability when thera‐ peutically delivered.

We highly acknowledged the interest and raised professional profile of all authors who have contributed to writing this book, and the academic and scientific support provided by Alina Crenguța Nicolae, PhD, who assisted our work during in whole period of the project.

> **Cristina Manuela Drăgoi and Alina Crenguța Nicolae** Faculty of Pharmacy "Carol Davila" University of Medicine and Pharmacy Bucharest, Romania

**Section 1**

**Molecular Biochemistry and Pharmacological**

**Mechanisms of Action of Melatonin and Its**

**Indole Derivatives**
