Cholinergic Basis for Alzheimer Therapy

486 Pages·1991·20.46 MB·English

by  Robert E. Becker (auth.)

Advances in Alzheimer Disease Therapy
Series Editors:
Ezio Giacobini
Robert Becker
This series periodically brings up-to-date advances in basic and clinical sciences
that are relevant to understanding the etiology, pathogenesis, diagnosis, and
treatment of Alzheimer disease. Experts from the various fields relevant to
understanding Alzheimer disease report their new research findings and
discuss the newest developments in possible Alzheimer disease therapies.
Cholinergic Basis
for Alzheimer Therapy
Robert Becker
Ezio Giacobini
Editors
Springer Science+ Business Media, LLC
Robert Becker Ezio Giacobini
Departr.nentofPsyclriatry Department of Pharmacology
School of Medicine School of Medicine
Southern lllinois University Southern lllinois University
Springfield, IL 62794 Springfield, IL 62794
U.S.A. U.S.A.
Library of Congress Cataloging-in-Publication Data
Cholinergic basis for Alzheimer therapy/edited by Robert Becker,
Ezio Giacobini.
p. cm.-(Advances in Alzheimer therapy)
Includes bibliographical references and index.
ISBN 978-1-4899-67404
1. Alzheimer's disease--Chemotherapy. 2. Cholinergic mechanisms.
3. Cholinesterase inhibitors--Therapeutic use. 4. Nerve growth factor
Therapeutic use. I. Becker, Robert E. II. Giacobini, Ezio ill. Series.
[DNLM: 1. Alzheimer's Disease--drug therapy. 2. Cholinesterase Inhibitors
therapeutic use. 3. Neuroregulators--therapeutic use. 4. Parasympathomi
metics--therapeutic use. 5. Receptors, Cholinergic-drug effects.]
RC523.C49 1991
616.8'31061-dc20
DNLM/DLC 9126122
for Library of Congress CIP
Printed on acid-free paper.
© Springer Science+ Business Media New York 1991
Originally published by Birkhliuser Boston in 1991
Softcover reprint of the hardcover 1st edition 1991
Copyright is not claimed for works of U.S. Government employees.
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ISBN 978-1-4899-6740-4 ISBN 978-1-4899-6738-1 (eBook)
DOI 10.1007/978-1-4899-6738-1
Camera-ready text prepared by the editors using WordPerfect 5.1 on an ffiM PS2
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CONTENTS
Introduction by the Editors: Therapy of the Cognitive Deficit
in Alzheimer's Disease: The Cholinergic System ............ 1
Robert Becker
Part I. Cholinesterases: Anatomy, Pathology
and Human Genetics
Cortical Cholinesterases in Alzheimer's Disease: Anatomical
and Enzymatic Shifts from the Normal Pattern ..... 25
M.-Marsel Mesulam and Changiz Geula
Cholinesterases in Human Degenerative Diseases . . . . . . . . . . 31
John R. Atack
The Pathology of the Human Nucleus Basalis of Meynert
and its Implications for a Specific Therapy . . . . . . . . . . 38
Thomas Arendt and Volker Bigl
Structure-Function Relationship Studies in Human
Cholinesterases as an Approach for Evaluating Potential
Pharmacotherapeutic and/or Toxicity Effects of Cholinergic Drugs . . • 46
Hermona Soreq, Yael Loewenstein, Lewis F. Neville,
Shlomo Seidman, Revital Ben-Aziz, Gal Ehrlich, Averell Gnatt,
Dalia Ginzberg and Haim Zakut
Structure of the Acetylcholinesterase Gene: Regulation
of its Expression . . . . . • . . . • • • • . . . . . . . . 53
Palmer Taylor, Ying Li, Shelley Camp, Tara L. Rachinsky
and Damon Getman
Part II. Pharmacokinetics and Neurophysiology of
Cholinesterase Inhibitors
Kinetics and Mechanisms of Reversible and Progressive
Inhibition of Acetylcholinesterase . . . . . . . . . . . . . . . . 63
Elsa Reiner, Vera Simeon and Mira Skrinjaric-Spoljar
v
Clinical Pharmacokinetics of Centrally Acting
Cholinesterase Inhibitors . . . . . . . . . . . . . . . . . . 68
Per Hartvig, Lars WiklWid, Sten Magnus Aquilonius
and Bjorn Lindstrom
Pre- and Postsynaptic Effects of Cholinesterase Inhibitors . . . . 74
Lev G. Magazanik, Vadim Y. Bolshakov, Nera Y. Kukomskaya,
Natalja N. Potapjeva, Marina V. Samojlova, Vladmir A. Snetkov,
Rashid A. Giniatullin and Jordi Molgo
Part III. Cholinergic Receptors, Immunocytochemistry
and PET Scanning
Immunocytochemistry of Muscarinic and Nicotinic Receptors
in Human Brain .. . . . . . 85
Hannsjorg SchrOder
Presynaptic Cholinergic Mechanisms in Human Cerebral
Cortex of Adult and Aged Patients . . . . . . . . . . . . . . . . 92
Mario Marchi, Elisabetta Besana, Agnese Codignola,
Paola Sanguineti, Maurizio Raiteri, Gian Carlo Andrioli
and Antonio Ruelle
Nicotinic Acetylcholine Receptors in the Human
Nervous System . . . . . . . . . . . . . . . . . . . . . . . 98
Bice Chini, Paola Tarroni, Francesca Rubboli,
Elena Raimondi and Francesco Clementi
Nicotinic Receptors in the CNS as Vtsualized by Positron
Emission Tomography . . . . . . . . . . . . . . . .... 107
Agneta Nordberg, Per Hartvig, Anders Lilja, Hans LWidqvist,
Ulrika Warpman, Johan Ulin, Bengt Ungstrom,
Kaarina Amberla, Matti Viitanen and Bengt Winblad
Part IV. Cholinergic System: Models of Alzheimer Disease,
Effects of Lesions and Aging
Nucleus Basalis Lesions and Recovery . . . . . . . . . . . . . . 119
Vahram HaroutWiian, William Wallace and Kenneth L. Davis
vi
Experimental Autoimmune Dementia (EAD ): An Immunological
Model of Memory Dysfunction and Alzheimer's Disease . . . . 126
Daniel M. Michaelson, Gil Alroy, Lior Soussan,
Joab Chapman and Joram Feldon
Aging of the Cholinergic Synapse in the Rat's Hippocampus:
Effect of Acetyl-L-Carnitine _. . . . . . . • • • . • • . . . . . 134
Luciano Angelucci, G. Sebastiano Alema, Assunta Imperato,
Massimo Castorina, M. Teresa Ramacci and M. Grazia Scrocco
SDAT Models and Their Dynamics .... 141
Alexander G. Karczmar
Part V. Cholinergic Pharmacotherapy: Toxicology and
Drug Effects on Learning and Memory
Toxicological Umitations to Cholinomimetic Therapy ........ 155
Bo R. Holmstedt and Ingrid Nordgren
Learning and Memory Enhancement by Drugs Which
Indirectly Promote Cholinergic Neurotransmission ........ 162
Harbans Lal and Michael J. Forster
Functional Cholinergic Receptor Sensitivity:
The Role of Drug Probes . . . • • . . . . . . . . . . . . . . . 170
Trey Sunderland, Susan Molchan, Ben Vitiello, Rick Martinez
and Alex Martin
Brain Phospholipids and Their Metabolites in Alzheimer's Disease:
Possible Role of "Auto-Cannibalism" and Implications for
Drug Development . . . . . . . . . . . . . . • . . . . . . . 183
Richard J. Wurtman, J. Krzysztof Blusztajn, Roger Nitsch
and John H. Growdon
Part VI. Non-Cholinomimetic Agents
Galanin: Regulation of Cholinergic Function and Behavior . . . . . . 193
Sven Ove Ogren and Aladdin Pramanik
Activation of Brain Cholinergic System by Noncholinomimetic Agents . . 200
Giancarlo Pepeu, Maria Grazia Giovannini, Fiorella Casamenti,
Carla Scali and Paola Rodino
vii
Part Vll. Cholinesterase Inhibitors:
The First Generation
Physostigmine in Alzheimer's Disease • . • . • • • . . . . 209
Leon J. Thai
Swedish Experiences ofTHA Therapy in Alzheimer's Disease • 216
Henrik Nyback, Arne Ahlin, Lars Gustafson and Lennart Minthon
Status ofTHA as Therapy for Alzheimer's Disease . 224
Serge Gauthier and Louise Gauthier
Responders and Nonresponders in Experimental Therapy
of Alzheimer's Disease • . • • • • • . • • • • • • . . . . • 231
Karl J. Alhainen, Paavo J. Riekkinen Jr., Hilkka S. Soininen,
Karl J. Reinikainen and Paavo J. Riekkinen Sr.
ChoUnesterase Inhibitors in Alzheimer's Disease:
Evaluation of Clinical Studies . • • • . . • . • • . . . . . . . . 238
Bengt Winblad, Abdu Adem, Lars Backman, Agneta Nordberg,
Fredrik Blinder and Peter Arhem
Part Vlll. Cholinesterase Inhibitors:
The Second Generation
The Second Generation of Cholinesterase Inhibitors:
Pharmacological Aspects . . . . . . • . • . . . • . . . • . . . 247
Ezio Giacobini
The Second Generation of Cholinesterase Inhibitors:
CUnical and Pharmacological Effects • • • . . . •••.• 263
Robert E. Becker, Pamela Moriearty and Latha Unni
Heptyl Physostigmine-Novel Acetylcholinesterase Inhibitor:
Biochemical and Behavioral Pharmacology . . . • • . . • . 297
L.L. Iversen, G. Bentley, G. Dawson, S.B. Freedman,
E.A. Harley, S.D. Iversen, N.MJ. Rupniak, S. Tye,
P.O. Pagella and PL. Rugarli
Clinical and Preclinical Studies with Huperzine . • •. 305
Israel Hanin, Xi Can Tang and Alan P. Kozikowski
E 2020: The Pharmacology of a Piperidine ChoUnesterase Inhibitor . . 314
Sharon L. Rogers, Yoshiharu Yamanishi and Kiyomi Yamatsu
viii
Pharmacodynamics of Oral E2020 and Tacrine in Humans:
Novel Approaches . • . . • . . . . . . . . . . . . . . . 321
Kathleen A. Shennan
Preclinical and Clinical Studies with Galanthamine . . . . . . . . . 329
Torben Thomsen, Helmut Kewitz. Ulrich Bickel,
Max Straschill and Gerhard Holl
Alzheimer Therapy with Cholinomimetics: The Japanese Experience .. 337
Mitsuo Yoshida
Part IX. Use of Cholinergic Agonists in Alzheimer Disease
Novel Muscarinic Agonists for Treatment of Alzheimer's Disease . . 347
Roy D. Schwarz, Linda L. Coughenour, Robert E. Davis,
David T. Dudley, Walter H. Moos, Michael R. Pavia and Haile Teele
New Muscarinic Agonists with Special Emphasis on AF102B .. 354
Abraham Fisher, Rachel Haring, David Gurwitz,
Claire M. Fraser, Zipora Pittel, Eliahu Heldman, lshai Karton,
Rachel Brandeis and Dov Barak
AF102B: Preclinical Experience . . . • . . . . . . . . . .. 363
Yoshinori Iga, Nobuo Ogane, Yasunari Saito, Sadao Samuraizono,
Gosei Kawanishi and Haruo Kobayashi
Muscarinic Agonists for Senile Dementia:
Past Experience and Future Trends . . . . . . . . . . . . . . . 370
Albert Enz, Julian A. Gray and Rene Spiegel
Part X. Effects of Nicotine and Nicotinic Agonists
Some Novel Actions of Nicotine in Nucleus Basalis
Lesioned Rats and in Hippocampal Slices . . . . . . . . . . 379
Nelida N. Sjak-Shie, Edwin M. Meyer and Bruce E. Hunter
New Nicotinic Agonists and Cerebral Blood Flow . . . . . . . . . . 386
Stephen P. Americ
Part XI. Nerve Growth Factors:
Potential for Alzheimer Disease Therapy
Pharmacological Actions of Recombinant Human Nerve Growth Factor
on Lesioned Central Cholinergic Neurons: Rationale for the
Treatment of Alzheimer's Disease . 397
Paul A. Lapchak and Franz Hefti
ix