The Histamine H3 Receptor, Volume 30: A Target for New Drugs (Pharmacochemistry Library, Volume 30)

In the early eighties when the H 3 receptor was identified, many thought that an H 3 ligand, an agonist or an antagonist, would become available as a therapeutic agent. This has not occurred. The reason for this could be the fact that many investigators consider histamine mainly, if not only, as a mediator present in for example mast cells being released during allergic events. However, it has become apparent that histamine is an important neurotransmitter. Its role in the nervous system, especially in the central part of it, is rather extensive. The H 3 receptor is mainly found as a presynaptic one, both on histaminergic neurons (the auto-type) and on other neuronal systems (the hetero-type). Both the H 3 agonist and the H 3 antagonist cause important pharmacological effects. Several ligands have become available now, including radiolabelled analogues. In this book, the current state of affairs with regards to the medicinal chemistry and pharmacology of the H 3 receptor and the several ligands available are presented by a number of experts in the field. The book presents an extended review of what has happened since the first H 3 paper appeared. The editors hope that publication of this work will lead to an increase in interest of both academia and industry for the H 3 receptor, especially as a target for drug development. Content: Editorial Board Page v Preface Page ix H. Timmerman, R. Leurs Subclassification of histamine receports, H 3 -receptor subtypes? Localization of H 3 receptors in the brain Original Research Article Pages 1-12 J-M. Arrang, S. Morisset, C. Pillot, J-C. Schwartz Modulation of in vitro neurotransmission in the CNS and in the retina via H 3 heteroreceptors Original Research Article Pages 13-26 E. Schlicker, M. Kathmann H 3 receptor modulation of the release of neurotransmitters in vivo Original Research Article Pages 27-40 P. Blandina, L. Bacciottini, M.G. Giovannini, P.F. Mannaioni H3 receptor modulation of neuroendocrine responses to histamine and stress Original Research Article Pages 41-58 Ulrich Knigge, Andreas Kj˦r, Henrik Jørgensen, Jørgen Warberg Functional role of histamine H 3 receptors in peripheral tissues Original Research Article Pages 59-111 G. Bertaccini, G. Coruzzi, E. Poli Biochemical properties of the histamine H 3 receptor Original Research Article Pages 113-126 Marcel Hoffmann, Henk Timmermann, Rob Leurs Radioligands for the histamine H 3 receptor and their use in pharmacology Original Research Article Pages 127-144 F.P. Jansen, R. Leurs, H. Timmerman Substituted imidazoles, the key to histaminergic receptors Original Research Article Pages 145-158 W.M.P.B. Menge, H. Timmerman Synthesis of radioligands for the histamine H 3 receptor Original Research Article Pages 159-174 Albert D. Windhorst, Rob Leurs, Wiro M.P.B. Menge, Henk Timmerman, Jacobus D.M. Herscheid Medicinal chemistry of histamine H 3 receptor agonists Original Research Article Pages 175-196 M. Krause, H. Stark, W. Schunack Medicinal chemistry of histamine H3 receptor antagonists Original Research Article Pages 197-222 James G. Phillips, Syed M. Ali Molecular modelling studies of histamine H 3 receptor ligands Original Research Article Pages 223-241 Iwan J.P. De Esch, Paul H.J. Nederkoorn, Henk Timmerman Brain histamine in pathophysiological conditions and brain diseases Original Research Article Pages 243-253 P. Panula, T. Sallmen, O. Anichtchik, K. Kuokkanen, M. Lintunen, J.O. Rinne, M. Mättö, J. Kaslin, K.S. Eriksson, K. Karlstedt Histamine H 3 antagonists as potential therapeutics in the CNS Original Research Article Pages 255-267 Kenji Onodera, Takehiko Watanabe Clinical application of HA H 3 receptor antagonists in learning and memory disorders Original Research Article Pages 269-286 C.E. Tedford Author index Page 287 Subject index Pages 289-291 In the early eighties when the H 3 receptor was identified, many thought that an H 3 ligand, an agonist or an antagonist, would become available as a therapeutic agent. This has not occurred. The reason for this could be the fact that many investigators consider histamine mainly, if not only, as a mediator present in for example mast cells being released during allergic events. However, it has become apparent that histamine is an important neurotransmitter. Its role in the nervous system, especially in the central part of it, is rather extensive. The H 3 receptor is mainly found as a presynaptic one, both on histaminergic neurons (the auto-type) and on other neuronal systems (the hetero-type). Both the H 3 agonist and the H 3 antagonist cause important pharmacological effects. Several ligands have become available now, including radiolabelled analogues. In this book, the current state of affairs with regards to the medicinal chemistry and pharmacology of the H 3 receptor and the several ligands available are presented by a number of experts in the field. The book presents an extended review of what has happened since the first H 3 paper appeared. The editors hope that publication of this work will lead to an increase in interest of both academia and industry for the H 3 receptor, especially as a target for drug development In the early eighties when the H3 receptor was identified, many thought that an H3 ligand, an agonist or an antagonist, would become available as a therapeutic agent. This has not occurred. This book presents the state of affairs with regards to the medicinal chemistry and pharmacology of the H3 receptor. Histamine is released in the brain from neurons projecting in a diffuse manner to widely divergent cerebral areas and arising from the tuberomammillary nucleus of the posterior hypothalamus.