Six decades after the serendipitous discovery of chlorpromazine
as an antipsychotic and four decades after the launch of clozapine,
the first atypical or second generation antipsychotic,
psychopharmacology has arrived at an important crossroad. It is
clear that pharmacological research and pharmaceutical development
must now focus on complementary or even alternative mechanisms of
action to address unmet medical needs, i.e. poorly treated domains
of schizophrenia, improved acceptance by patients, better adherence
to medication, safety in psychoses in demented patients, and
avoiding cardiac and metabolic adverse effects. The first
completely novel mechanisms evolving from our insights into the
pathophysiology of psychotic disorders, especially the role of
glutamatergic mechanisms in schizophrenia, are now under
development, and further principles are on the horizon. This
situation, in many respects similar to that when the initial
second-generation antipsychotics became available, can be rewarding
for all. Preclinical and clinical researchers now have the
opportunity to confirm their hypotheses and the pharmaceutical
industry may be able to develop really novel classes of
therapeutics.
When we were approached by the publishers of the Handbook of
Experimental Pharmacology to prepare a new volume on
antipsychotics, our intention was to capture both, the accumulated
preclinical and clinical knowledge about current antipsychotics as
well as prospects for new and potentially more specific
antischizophrenia principles. These efforts should be based on the
pathophysiology of the diseases and the affected neurotransmitter
systems. Since preclinical research on antipsychotic compounds is
only reliable when intimately linked through translational aspects
to clinical results, we decided to include clinical science as
well. It turned out that that this endeavor could not be covered by
a single volume. We thank the editorial board and the publishers
for supporting our decision to prepare two volumes: Current
Antipsychotics and Novel Antischizophrenia Treatments. These topics
cannot really be separated from one another and should be seen as a
composite entity despite the somewhat arbitrary separation of
contributions into two volumes. The continuing challenges of
developing improved and safer antipsychotic medications remain of
concern and are discussed in the first volume. The new
opportunities for the field to develop and license adjunctive
treatments for the negative symptoms and cognitive deficits that
are treated inadequately by existing compounds have been
incentivized recently and provide the focus for the second volume.
We hope these collective contributions will facilitate the
development of improved treatments for the full range of
symptomatology seen in the group of schizophrenias and other major
psychotic disorders.
Gerhard Gross, Ludwigshafen, Germany
Mark A. Geyer, La Jolla, CA
This volume will try to put current therapy - achievements,
shortcomings, remaining medical needs - and emerging new targets
into the context of increasing knowledge regarding the genetic and
neurodevelopmental contributions to the pathophysiology of
schizophrenia. Some of the chapters will also deal with respective
experimental and clinical methodology, biomarkers, and
translational aspects of drug development. Non-schizophrenia
indications will be covered to some extent, but not
exhaustively."
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