The Histamine H3 Receptor: A Target for New Drugs

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. 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 H3 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 H3 agonist and the H3 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 H3 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 H3 paper appeared. The editors hope that publication of this work will lead to an increase in interest of both academia and industry for the H3 receptor, especially as a target for drug development.

Preface. Subclassification of histamine receptors, H3-receptor subtypes? Localization of H3 receptors in the brain (J.M. Arrang et al.). Modulation of in vitro neurotransmission in the CNS and in the retina via H3 heteroreceptors (E. Schlicker, M. Kathmann). H3 receptor modulation of the release of neurotransmitters in vivo (P. Blandina et al.). H3 receptor modulation of neuroendocrine responses to histamine and stress (U. Knigge et al.). Functional role of histamine H3 receptors in peripheral tissues (G. Bertaccini et al.). Biochemical properties of the histamine H3 receptor (M. Hoffman et al.). Radioligands for the histamine H3 receptor and their use in pharmacology (F.P. Jansen et al.). Substituted imidazoles, the key to histaminergic receptors (W.M.P.B. Menge, H. Timmerman). Synthesis of radioligands for the histamine H3 receptor (A.D. Windhorst et al.). Medicinal chemistry of histamine H3 receptor antagonists (J.G. Phillips, S.M. Ali). Molecular modelling studies of histamine H3 receptor ligands (I.J.P. de Esch et al.). Brain histamine in pathophysiological conditions and brain diseases (P. Panula et al.). Histamine H3 antagonists as potential therapeutics in the CNS (K. Onodera, T. Watanabe). Clinical application of HA H3 receptor antagonists in learning and memory disorders (C.E. Tedford).