Pharmacochemistry Library – serie

Stable isotope techniques offer advantages in safety, sensitivity, specificity, and economy for many types of pharmaceutical investigations when compared to conventional techniques. Nevertheless, pharmaceutical researchers are slow to embrace stable isotope techniques.

This book assembles in one place comprehensive reviews of the many applications of stable isotopes and the background material necessary to understand the application. This approach is a deliberate attempt to encourage the usage of stable isotopes in pharmaceutical research. A bonus to the reader is the high standard of contributions from a very talented and diverse group of investigators.

This volume of Pharmacochemistry Library comprises the text of invited lectures presented at the 11th Noordwijkerhout-Camerino Symposium Trends in Drug Research, held in Noordwijkerhout, The Netherlands, from 11-15 May 1997.

In the programme attention has been given to the generation of new biological target systems and the generation of new lead molecules, with presentations on e.g. combinatorial chemistry, compound libraries, database search, high throughput screening and molecular biology.

Other topics discussed were the perspectives for new medicines for the gastro-intestinal tract, the major developments in the search for effective anti-HIV drugs and new aspects in synthetic approaches. In a special session three topics which currently draw much attention were discussed: How to deal with the major problem of resistance against antimirobial agents? Can the apoptosis mechanism be used as a drug target? Is the newly observed phenomenon of inverse agonism a general principle and has it consequences for drug development (and use?)

Vaso-occlusive disorders including unstable angina, myocardial infarction, transient ischemic attacks, stroke and peripheral artery disease remain the major sources of morbidity and mortality in western civilization. Platelet activation and resulting platelet aggregation play a major role in the pathogenesis of these thromboembolic diseases. Recognition of the contribution of platelets to the pathophysiology of cardiovascular disease has provided impetus for the continued search for new antiplatelet agents. Hence, over the past two decades many strategies have been evaluated in the search for efficacious mechanisms to reduce platelet function. The medical need for more efficacious antithrombotic drugs and the growing understanding of the role of platelets in vascular injury have catalyzed the extensive evaluation of novel approaches to control platelet function. Along these lines, the volume therefore provides an in-depth assessment of ongoing clinical trials, new and clinically established agents, and other developments in this rapidly developing field.

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.