Winifred G. Nayler – författare

This is the first book to summarize experimental results from the new, rapidly expanding field of research into the calcium channel in cell membrane. Calcium is an ubiquitous messenger of various cellular functions. Its fundamental role in the regulation of cardiac contractions has long been recognized. Drugs counteracting some actions of calcium ions, namely calcium antagonists, have since become essential to research. In the last decade it has been established that calcium ions reach their target intracellular system by passing through specialized calcium channels in the membrane. Recently improved experimental techniques combined with the discovery of highly specific Ca channel ligands have dramatically enlarged our knowledge of the molecular structure and function of such channels. The contributions by leading world specialists shed new light on both basic science and possible clinical implications for cardiovascular pharmacology, endocrinology and neuropharmacology.

Dieses Buch gibt einen hervorragenden Überblick über den Stand der wissenschaftlichen Forschungen auf dem Gebiet der Pharmakologie der Calcium-Antagonisten. Die Pharmakokinetik der verschiedenen Calcium-Antagonisten wird ebenso beschrieben, wie die Anwendung in der Praxis bei den verschiedensten Erkrankungen des Herz-Kreislauf-Systems. Nebenwirkungen, Risiken und Kontraindikationen sind ein weiteres wichtiges Thema. Zum Schluß wird ein Ausblick auf die Zukunft dieses vielseitigen Medikamentes gegeben.

"Another damned, thick, square book! Always scribble, scribble, scribble! Eh! Mr. Gibbon?" From the Literary Memoirs of Willi­ am, DUKE OF GLOUCESTER, 1743-1805 The foreword of any book is probably the most difficult to write -not only because it stands at the beginning of an exercise in writing and logic but because it is in this chapter that areader can expect to find a clear and unambiguous explanation of the author's reason for writing the book and why some subject matter has been included and other subject matter excluded. Potential readers ofthis book may not have an inclination to question why some subject matter has been excluded but instead may wonder why another book on calcium antagonists has been published. However, it is arguable with some force that there have been at least three recent developments in the field of calcium antagonism which provide more than adequate support for the view that another book on this topic is warranted. These developments include: (i) an improved understanding of the chemical structure, mode of action and architecture of the voltage-activated, calcium antagonist-sensitive calcium channels and their associated calcium-antagonist specific binding sites; (ii) a more accurate appreciation ofhow and when the calcium antagonists should be used in the management of a variety of clinical dis orders including cerebral ischaemia atherosclerosis, "mild" ischaemic heart disease, ventricular hyper­ trophy, impaired ventricular relaxation and hypertension (to name but a few), and (iii) the emergence of a second generation of calcium antagonists.

"Schon wieder so ein verdammtes, dickes, spießiges Buch! Immer kritzeln, kritzeln, kritzeln, nicht wahr, Mr. Gibbon!" Aus den Literarischen Memoiren von Herzog Wilhelm von Gloucester, 1743-1805 Bei jedem Buch ist das Vorwort wahrscheinlich das Schwierigste. Nicht nur weil es am Beginn einer Übung im Schreiben und im folgerichtigen Denken steht, sondern weil der Leser an dieser Stelle eine eindeutige Erklärung dafür erwarten kann, warum das Buch überhaupt geschrie­ ben wurde und warum manche Themen besprochen, andere hingegen weggelassen wurden. Mancher Leser wird sich vielleicht keine Gedanken darüber machen, warum der eine oder andere Punkt nicht erwähnt wurde; er wird sich vielmehr fragen, warum schon wieder ein Buch über Calciumantagoni­ sten erscheint. Ich glaube aber, es kann mit Fug und Recht behauptet werden, daß auf diesem Gebiet in der letzten Zeit zumindest drei Ent­ wicklungen zu verzeichnen waren, welche die Veröffentlichung eines neuen Buches zu diesem Thema unbedingt gerechtfertigt erscheinen las­ sen: I. Wir wissen heute mehr über die chemische Struktur, die Wirkungs­ weise und den Aufbau der spannungsempfindlichen, auf Calcium­ antagonisten ansprechenden Calcium-Kanäle und ihre für Calcium­ antagonisten spezifischen Bindungsstellen. II. Die Anwendungsmöglichkeiten von Calciumantagonisten zur Be­ handlung einer Vielfalt von Erkrankungen wie zerebrale Ischämie, Atherosklerose, "leichte" ischämische Herzkrankheit, Linksherz­ hypertrophie, beeinträchtigte ventrikuläre Relaxation und Hyper­ tonie, um nur einige zu nennen, können heute besser beurteilt wer­ den. 111. Eine zweite Generation von Calciumantagonisten ist jetzt verfügbar.

"Those who choose to increase their knowledge still further by reading ... will discover an exciting new world. " NOEL WHITTAKER, in "Making Money Made Simple" 1989. The development of calcium antagonists has recently been described as representing "one of the major advances in cardiovascular thera­ peutics of the latter half of the twentieth century" (Braunwald, 1990). However, although the development of these drugs started in the mid­ nineteen sixties it is only recently that their real potential has begun to be appreciated. Even now the calcium antagonist saga is not complete, since new compounds continue to appear and new therapeutic applica­ tions emerge. Based on the experience gained in the clinics in which these drugs have been used recognition is being given now to the need to improve upon the prototypes of the group. Such improvement is resulting in the development and production not only of long-acting formulations of the prototypes (nifedipine, verapamil and diltiazem) but also of new calcium antagonists with improved tissue selectivity, potency and duration of action. To those of us who are interested in this field such a development is both exciting and rewarding. As far as the clinicians who prescribe these drugs are concerned the long-acting nature of some of the newer calcium antagonists should make the satisfactory management of their patients an achievable goal.

This is the first book to summarize experimental results from the new, rapidly expanding field of research into the calcium channel in cell membrane. Calcium is an ubiquitous messenger of various cellular functions. Its fundamental role in the regulation of cardiac contractions has long been recognized. Drugs counteracting some actions of calcium ions, namely calcium antagonists, have since become essential to research. In the last decade it has been established that calcium ions reach their target intracellular system by passing through specialized calcium channels in the membrane. Recently improved experimental techniques combined with the discovery of highly specific Ca channel ligands have dramatically enlarged our knowledge of the molecular structure and function of such channels. The contributions by leading world specialists shed new light on both basic science and possible clinical implications for cardiovascular pharmacology, endocrinology and neuropharmacology.

Dieses Buch gibt einen hervorragenden Überblick über den Stand der wissenschaftlichen Forschungen auf dem Gebiet der Pharmakologie der Calcium-Antagonisten. Die Pharmakokinetik der verschiedenen Calcium-Antagonisten wird ebenso beschrieben, wie die Anwendung in der Praxis bei den verschiedensten Erkrankungen des Herz-Kreislauf-Systems. Nebenwirkungen, Risiken und Kontraindikationen sind ein weiteres wichtiges Thema. Zum Schluß wird ein Ausblick auf die Zukunft dieses vielseitigen Medikamentes gegeben.

"What we call the beginning is often the end, and to make an end is to make a beginning. The end is where we start from." T. S. ELIOT, "Geroniton" The discovery of endothelin-l was both an end and a beginning. It is an end because this discovery has started a plethora of investigations as to endothe1in''s sites of production, mode of action, it''s normal and abnormal physiological role and its involvement in a variety of pathological conditions ranging from renal failure to myocardial infarction, cardiac hypertrophy, hyperten­ sion, cyclosporine induced toxicity, mental depression, renal failure, stress related illness, and even stroke and sudden death. It is a beginning because no one can foresee where the investigations will ultimately lead, or how they will end. The discovery of the endothelins was a very recent event and soon specialist books will start to appear dealing in detail with different aspects of their chemistry, physiological role and pathological importance. The present book is intended to act as a guide and primer for those who are becoming intrigued by the many endothelin­ related articles which are now appearing in the journals but who as yet have not had the time or opportunity to be caught up in the web of enthusiasm and excitement which is motivating those more directly involved in the field of research.

"What we call the beginning is often the end, and to make an end is to make a beginning. The end is where we start from." T. S. ELIOT, "Geroniton" The discovery of endothelin-l was both an end and a beginning. It is an end because this discovery has started a plethora of investigations as to endothe1in's sites of production, mode of action, it's normal and abnormal physiological role and its involvement in a variety of pathological conditions ranging from renal failure to myocardial infarction, cardiac hypertrophy, hyperten­ sion, cyclosporine induced toxicity, mental depression, renal failure, stress related illness, and even stroke and sudden death. It is a beginning because no one can foresee where the investigations will ultimately lead, or how they will end. The discovery of the endothelins was a very recent event and soon specialist books will start to appear dealing in detail with different aspects of their chemistry, physiological role and pathological importance. The present book is intended to act as a guide and primer for those who are becoming intrigued by the many endothelin­ related articles which are now appearing in the journals but who as yet have not had the time or opportunity to be caught up in the web of enthusiasm and excitement which is motivating those more directly involved in the field of research.

"Those who choose to increase their knowledge still further by reading ... will discover an exciting new world. " NOEL WHITTAKER, in "Making Money Made Simple" 1989. The development of calcium antagonists has recently been described as representing "one of the major advances in cardiovascular thera­ peutics of the latter half of the twentieth century" (Braunwald, 1990). However, although the development of these drugs started in the mid­ nineteen sixties it is only recently that their real potential has begun to be appreciated. Even now the calcium antagonist saga is not complete, since new compounds continue to appear and new therapeutic applica­ tions emerge. Based on the experience gained in the clinics in which these drugs have been used recognition is being given now to the need to improve upon the prototypes of the group. Such improvement is resulting in the development and production not only of long-acting formulations of the prototypes (nifedipine, verapamil and diltiazem) but also of new calcium antagonists with improved tissue selectivity, potency and duration of action. To those of us who are interested in this field such a development is both exciting and rewarding. As far as the clinicians who prescribe these drugs are concerned the long-acting nature of some of the newer calcium antagonists should make the satisfactory management of their patients an achievable goal.