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1949stone

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[资源] Drug Discovery and Evaluation: Pharmacological Assays

Drug Discovery and Evaluation: Pharmacological Assays

The third edition of the book Drug Discovery and Evaluation. Pharmacological
Assays is presented here.
The volume of data has risen considerably compared to the second edition. In
particular, a large number of assays have been added. Meanwhile, data on Safety
Pharmacology have been removed from this edition. An extended discussion of that
important aspect of pharmacology was published in the book Drug Discovery and
Evaluation. Safety and Pharmacokinetic Assays, edited by H. G. Vogel, F. J. Hock,
J. Maas, and D. Mayer, by Springer in 2006.
Several of my colleagues provided essential contributions to this edition. In particular
I am indebted to S. A. Mousa for rewriting the chapter Pharmacological
Assays in Thrombosis and Hemostasis, S. G. E. Hart, for rewriting the chapter Activity
on Urinary Tract, G. Müller for rewriting and amending the chapter Antidiabetic
Activity, B. Schultz for amending the chapter Ophthalmologic Activity, and
J. Sandow for rewriting the chapter Endocrinology. All chapters have been revised
and thoroughly updated as well.
The approach to drug discovery is changing continuously. Decades ago, many
drugs were found by serendipity in clinical trials. Most new drugs, however, were
found by the classical approach in animal experiments. This approach has the advantage
of relatively high predictability, but it also has the disadvantage that little
information is provided about the molecular mechanisms involved in the observed
effects, and the detection of drugs with new mechanisms always required new models.
It is generally believed that the costs of developing new pharmaceutical drugs
are exploding, while the output of new drugs is actually decreasing. A change
in paradigm, the target-based or mechanism-based drug discovery approach, was
therefore welcomed with great enthusiasm. The techniques of combinatorial chemistry
could generate thousands of compounds to be tested against thousands of targets
using high-throughput and ultra-high-throughput technology with tremendous
capacity. This made it highly effective for the identification of target-selective compounds.
However, despite the fact that this approach is very advantageous from a
scientific and practical viewpoint, it did not translate into a high success rate in the
discovery of new drugs. This has naturally led to questions regarding the success of
target-based drug discovery and, more importantly, a search for alternatives.
The target-based approach has therefore been replaced again by the physiologybased
approach, the classical drug discovery paradigm, or the function-based approach,
which seeks to induce a therapeutic effect by normalizing a disease-specific
abnormality.
On top of this, important changes in the management of some of the larger drug
companies have taken place in recent years. Modern managers were installed as
chief executive officers and other high-level executives, quite often with little or
no biological and technical experience. They were more interested in blockbusters
and in shareholders’ value than finding new drugs, especially for rare diseases.
Research workers were confronted with cumbersome and inflexible organizational
structures characterized by regimentation, control, conformity, and excessive bureaucracy.
Consequently, creativity and productivity decreased in this environment.
Recently, however, there are signs that the situation is changing.
In this book we ask the question: “Quo vadis, pharmacology?” We suggest giving
pharmacologists the freedom, time, and money to carry out their own ideas.
We also describe animal models of rare diseases that enable the medically trained
pharmacologist to find appropriate drugs.
We are well aware that the rapid progress in biology will once again change the
methodological approach in the coming years, and that electronicmedia will continuously
help the researcher to access and share information. However, it is becoming
more and more evident that many young pharmacologists have only limited training
in classical pharmacological methodologies.When searching for these methods,
researchers will only find insufficient information on the methodological details in
the electronic databases currently available. To this end, we hope the current book
may bridge this gap by comprehensively covering those pharmacological methods
utilized for over more than a hundred years.
At this point I would like to express my sincere thanks to all colleagues who
contributed to the new and to the earlier editions of this book. Their names and
affiliations are given in alphabetical order.
Spring 2007 H. Gerhard Vogel
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