The Third Histamine Receptor: Selective Ligands as Potential Therapeutic Agents in CNS Disorders

408 Pages·2008·4.6 MB·English

by  Divya Vohora

The
Third Histamine
Receptor
Selective Ligands as
Potential Therapeutic Agents in
CNS Disorders
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The
Third Histamine
Receptor
Selective Ligands as
Potential Therapeutic Agents in
CNS Disorders
Editor
Divya Vohora
Boca Raton London New York
CRC Press is an imprint of the
Taylor & Francis Group, an informa business
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Library of Congress Cataloging-in-Publication Data
The third histamine receptor : selective ligands as potential therapeutic agents in CNS
disorders / edited by Divya Vohora.
p. ; cm.
Includes bibliographical references and index.
ISBN-13: 978-1-4200-5392-0 (hardcover : alk. paper)
ISBN-10: 1-4200-5392-2 (hardcover : alk. paper)
1. Histamine--Receptors. 2. Central nervous system--Diseases--Chemotherapy. 3.
Antihistamines. I. Vohora, Divya.
[DNLM: 1. Histamine H3 Antagonists--therapeutic use. 2. Central Nervous System
Diseases--drug therapy. 3. Receptors, Histamine H3--metabolism. QV 157 T445 2009]
QP801.H5T53 2009
612.8’2--dc22 2008019288
Visit the Taylor & Francis Web site at
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and the CRC Press Web site at
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Contents
Preface .....................................................................................................................vii
Editor ........................................................................................................................ix
Contributors ..............................................................................................................xi
SECTION A Introduction
Chapter 1 H Receptor Target: Past, Present, and Future
3
Perspectives from Worldwide H Experts ............................................3
3
Divya Vohora, Andrew D. Medhurst, Nicholas I. Carruthers,
and Sylvain Celanire
Chapter 2 Third Histamine Receptor: From Discovery
to Clinics, Long-Lasting Love Story at INSERM
and Bioprojet ......................................................................................13
Jean-Charles Schwartz
Chapter 3 Histamine as Neurotransmitter ..........................................................31
Oliver Selbach and Helmut L. Haas
SECTION B The Third Histamine Receptor
Chapter 4 Phylogeny, Gene Structure, Expression, and Signaling .....................83
Pertti Panula, CongYu Jin, Kaj Karlstedt,
and Remko A. Bakker
Chapter 5 Drug Discovery: From Hits to Clinical Candidates .........................103
Sylvain Celanire, Florence Lebon, and Holger Stark
Chapter 6 Peripheral Actions and Therapeutic Potential
in Periphery ......................................................................................167
Gabriella Coruzzi and Maristella Adami
v
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vi Contents
SECTION C Therapeutic Potential in Central
Nervous System Disorders
Chapter 7 Cognitive Functions, Attention-Defi cit Hyperactivity
Disorders, and Alzheimer’s Disease ................................................213
Maria Beatrice Passani, Patrizio Blandina, Kaitlin E.
Browman, and Gerard B. Fox
Chapter 8 Sleep Disorders.................................................................................241
Jonathan E. Shelton, Timothy W. Lovenberg,
and Christine Dugovic
Chapter 9 Obesity .............................................................................................277
Timothy A. Esbenshade, Michael E. Brune,
and Marina I. Strakhova
Chapter 10 Epilepsy ............................................................................................305
Divya Vohora and Krishna K. Pillai
Chapter 11 Schizophrenia ...................................................................................329
Kaitlin E. Browman, Min Zhang, Gerard B. Fox,
and Lynne E. Rueter
Chapter 12 Other Central Nervous System Diseases and Disorders ..................355
Paul L. Chazot and Fiona C. Shenton
Index ..........................................................................................................371
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Preface
The third histamine receptor, identifi ed in 1983, generated widespread interest as
a potential target for its extensive role in the central nervous system (CNS). The
fi rst book on this subject, edited by Leurs and Timmerman, was available in 1998.
H owever, many advances have taken place since then. Molecular advances in the
past few years followed by cloning of human H receptors and development of a large
3
number of selective and nonimidazole H receptor antagonists with pharmacological
3
evidence in a number of different therapeutic conditions raise the hope for having
an H receptor-related drug to hit the market soon. In this book, an attempt has been
3
made to bring together worldwide scientists actively involved in the H fi eld both
3
from academia and from pharmaceutical industry including medicinal and com-
putational chemists, biologists, and pharmacologists. This book aims to provide a
single source of information from the identifi cation and localization of H receptor
3
to the development of novel ligands incorporating preclinical and more recent clini-
cal studies, indicating the earliest possible stage of development of these ligands.
It is a blend of almost all the therapeutic activities being explored for these ligands
with literature from studies using cutting-edge research techniques as well as patent
literature.
The format is organized to provide the readers with the introduction of the fi eld
starting with the expert opinion in the light of knowledge available with discussion
on the pitfalls and key issues related to H receptor research. One of the key features
3
of this section is that it incorporates suggestions from leading International experts
in the fi eld. It is hoped that these suggestions would provide directions for future
research for scientists involved in drug development. The introductory section con-
tinues with the history of the fi eld by one of the pioneers of the fi eld, the discoverers
of histamine H receptor, Professor J. C. Schwartz from Bioprojet, France, and a
3
general overview of histamine as a neurotransmitter in the brain by a very emi-
nent scientist, Professor H. L. Haas from Heinrich-Heine University, Düsseldorf,
Germany. This is followed by a chapter on H receptor phylogeny, gene structure,
3
and signaling. The selective ligands developed so far by different research groups
along with details of the stages of development are discussed in the next chapter.
A separate chapter is devoted to the peripheral actions of H receptors and the thera-
3
peutic potential of these ligands in the periphery. Subsequent chapters describe vari-
ous CNS disorders in which H receptors are known to have a major role including
3
cognitive functions, attention-defi cit hyperactivity disorder, Alzheimer’s disease,
sleep disorders, obesity, epilepsy, schizophrenia, depression, nociception, and neu-
rodegeneration. Each chapter addresses issues relevant to drug development.
Hopefully this book will be a valuable source of information for researchers
entering the fi eld of histamine research and will provide a comprehensive resource
for those already in this fi eld. This book is expected to generate interest among
the scientifi c community and is intended to benefi t both academic and i ndustrial
vii
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viii Preface
r esearchers from various disciplines including physiologists, biochemists, pharma-
cologists, and others.
I am indebted to all the contributors (30 eminent scientists from 14 organizations
located in 9 countries), who accepted my request and enabled the publication of this
book. Special thanks are due to Professors Schwartz and Haas, who, despite being
busy, squeezed their schedules and agreed to submit their valuable contributions.
Dr. Sylvain Celanire, leader of the histamine H project at the UCB Center for CNS
3
innovation, Belgium, helped in this venture in many ways. I appreciate the time and
effort he invested, and I express my gratitude for the same. Thanks and regards are
due to Professor Pillai, Head of the Department of Pharmacology, Jamia Hamdard,
New Delhi, who introduced me to this fi eld of H receptors way back in 1998. I thank
3
my husband and my daughter for their love and support.
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Editor
Dr. Divya Vohora (Shangari) received her masters in 1997 and doctorate in
2001 in pharmacology from Jamia Hamdard, New Delhi, where she joined as a
faculty member in 1999 and is currently working as a reader in the Department of
Pharmacology. Her research interests include pharmacology of the central nervous
s ystem with particular emphasis on epilepsy, cognitive functions, neurodegenerative
diseases, and histamine. She developed interest in the H receptor fi eld in 1998 when
3
she investigated the role of brain histamine and H receptor ligands in m odulating
3
both experimental seizures and action of antiepileptic drugs. She has worked as a
principal investigator in many funded research projects and has received grants from
All India Council for Technical Education (AICTE), Indian Council of Medical
Research (ICMR), University Grants Commission (UGC), Council of S cientifi c and
Industrial Research (CSIR), and Department of Science and T echnology (DST),
Government of India. She has supervised eight masters and three doctoral theses
and has received awards of national distinction including Career Award for Young
Teachers, Fast Track Award for Young Scientists, and Chandra Kanta Dandiya Prize
in pharmacology. She has authored more than 60 papers in national and interna-
tional journals with more than 100 citations.
ix
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