It is clear that the melanocortins are of immense academic interest. Further, these molecules have remarkable potential as pharmaceutical agents for treatment of multiple human and veterinary disorders and diseases. The evidence to support academic interest and clinical applications lies in significant part within the chapters of this book, chapters written by noted experts in the field who have worked diligently to understand the molecules and to move them toward clinical applications. I personally believe that the - MSH molecule and its derivatives will be used as routine therapeutics in the very near future. My belief is so strong that I left academia to form a company based on -MSH analogs and have caused millions of dollars to be spent on melanocortin research. Now why would a sane professor pick up such a challenge and enter business, an essential step toward any clinical application? It is the - MSH story that drove me. Consider that - MSH occurs in exactly the same amino acid sequence in humans and in the sea lamprey, an organism unchanged since its appearance during the Pennsylvanian period of the Paleozoic era (about 300 million years ago-way before dinosaurs were to be considered). There is unpublished evidence that the stability of the molecule can be traced back a half billion years. Frankly, I believe that the molecule existed even when single cells began to live together.

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ANNA CATA NIA, MD, PhD is a director of Center for Preclinical Investigation at Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy. She received her degree in Medicine and Surgery at the University of Milan and postdoctoral degree in Endocrinology and Metabolism at the University of Genoa, Italy. For over a decade she has been visiting scientist at The University of Texas Southwestern Medical Center at Dallas, Texas. During the past 20 years, her research activity has been focused on molecular biology and preclinical testing of melanocortins.

1. Structurea¿`Activity Relationships (SAR) of Melanocortin and Agoutia¿`Related (AGRP) Peptides Anamika Singh, Erica M. Haslach and Carrie Haskella¿`Luevano Abstract Introduction Structure and Chemistry of Melanocortin Peptides Structurea¿`Activity Relationships (SAR) Agoutia¿`Related Protein (AGRP) Development of Chimeric Peptide Analogues Conclusion 2. Melanocortin Signalling Mechanisms Paula C. Eves and John W. Haycock Abstract Introduction Melanocortin Receptors Melanocortins and Pigmentation Melanocortin Antia¿`Inflammatory and Immunomodulatory Roles Intracellular Signalling of Melanocortin Peptides Melanocortin Receptor Antagonists and Agonists Conclusion 3. Distribution and Function of Melanocortin Receptors within the Brain Kathleen G. Mountjoy Abstract Introduction MC1R Is Expressed in the Periaqueductal Gray and the MC1R Regulates Pain and Analgesia MC2R Is Expressed in Teleost Fish Brain and Fetal Mouse Brain, but Not in Adult Mammalian Brain MC3R Is Specifically Expressed in Hypothalamus and the Limbic System Where Its Functions Are Not Clearly Understood MC4R Is Expressed in Distinct Nuclei in Every Region of the Brain Reflecting It¿s Many Diverse Functions in the Brain MC5R Expression and Function in the Brain Is Unclear Melanocortin Receptor Accessory Proteins (MRAPs) Conclusion 4. Drugs, Exercise, and the Melanocortina¿`4 Receptora¿'Different Means, Same Ends: Treating Obesity Jay W. Schaub, Erin B. Bruce, and Carrie Haskella¿`Luevano Abstract Introduction Melanocortins Exercise Conclusion 5. Melanocortins in Brain Inflamation: The Role of Melanocortin Receptor Subtypes Ruta Muceniece and Maija Dambrova Abstract Introduction Distribution of MC Expressing Neurons and MC Receptors in the Brain MCR Subtypes and Brain Inflammation Main Intracellular Signalling Pathways of MC Receptors Potential Therapeutic Applications of MC Receptor Subtype Selective Compounds Conclusion 6. Melanocortins and the Cholinergic Antia¿`Inflamatory Pathway Daniela Giuliani, Alessandra Ottani, Domenica Altavilla, Carla Bazzani, Francesco Squadrito and Salvatore Guarini Abstract Introduction The Inflammatory Reflex Antishock Effects of Melanocortins Melanocortins Reverse Circulatory Shock through Activation of the Cholinergic Antia¿`Inflammatory Pathway Protective Effect of Melanocortins in Myocardial Ischemia/Reperfusion Melanocortins Prevent Myocardial Ischemia/Reperfusiona¿`Induced Damage through Activation of the Cholinergic Antia¿`Inflammatory Pathway Neuroprotection by Melanocortins in Ischemic Stroke Melanocortins Produce Neuroprotection Against Ischemic Stroke by Activating the Cholinergic Antia¿`Inflammatory Pathway Conclusion 7. Melanocortin Control of Cell Traficking in Vascular Inflamation Hetal B. Patel, Giovanna Leoni, Trinidad Montero Melendez, Andre L.F. Sampaio and Mauro Perretti Abstract Introduction Inflammation: Cell Trafficking and Microcirculation Melancortins in Experimental Inflammation Effects of Melanocortins on Inflammatory Cells In Vitro Lessons from Melanocortin Knockout Mice Drug Discovery Melanocortin Peptide Pharmacology Conclusion 8. Terminal Signal: Antia¿`Inflamatory Efects of αa¿`Melanocytea¿`Stimulating Hormone Related Peptides Beyond the Pharmacophore Thomas Brzoska, Markus Böhm, Andreas Lügering, Karin Loser and Thomas A. Luger Abstract Introduction αa¿`MSH Related Peptides and Melanocortin Receptorsa¿'Mediation of Antia¿`Inflammatory Effects? Antia¿`Inflammatory Effects of αa¿`MSH Related Tripeptides In Vitro and Vivo Therapeutic Potential of αa¿`MSHa¿`Related Tripeptides in Human Immunea¿`Mediated Inflammatory Diseases Conclusion 9. Protective Efects of Melanocortins in Systemic Host Reactions Stefano Gatti, Caterina Lonati, An ...