Volume 42 of "Progress in Drug Research" contains seven reviews and the various indexes which facilitate its use and establish the con nection with the previous volumes. The articles in this volume deal with organization and management of drug research; luteinizing hor mone regulators; natural products as anticancer agents; flavonoids and their pharmacological activity; serenics in the control of mental disturbances; Transfer Factor and its application and with Transfer Factor in malignancy. In the 34 years that "Progress in Drug Research" has existed, the Edi tor has enjoyed the valuable help and advice of many colleagues. Readers, the authors of the reviews, and last but not least, the review ers have all contributed greatly to the success of this series. Although the comments received so far have generally been favorable, it is nevertheless necessary to analyze and to reassess the current position and the future direction of such a review series. So far, it has been the Editors intention to help disseminate informa tion on the vast domain of drug research, and to provide the reader with a tool with which to keep abreast of the latest developments and trends. The reviews in PDR are useful to the non-specialists, who can obtain an overview of a particular field of drug research in a rela tively short time."

S. Ren and E.J. Lien: CaCo-2 cell permeability vs human gastrointestinal absorption: QSPR analysis.- J.C.G. Halford and J.E. Blundell: Pharmacology of appetite suppression.- B. Olivier, W. Soudijn and I. van Wijngaarden: Serotonin, dopamine and norepinephrine transporters in the central nervous system and their inhibitors.- D. Poyner, H. Cox, M. Bushfield, J.M. Treherne and M.K. Demetrikopoulos: Neuropeptides in drug research.- M. Kumari and M.K. Ticku: Regulation of NMDA receptors by ethanol.- H. Horikoshi, T. Hashimoto and T. Fujiwara: Troglitazone and emerging glitazones: new avenues for potential therapeutic benefits beyond glycemic control.- Rosamund C. Smith and Simon J. Rhodes: Applications of developmental biology to medicine and animal agriculture

Founded in 1959 by its current Editor, the series has moved from its initial focus on medicinal chemistry to a much wider scope. Today it encompasses all fields concerned with the development of new therapeutic drugs and the elucidation of their mechanisms of action, reflecting the increasingly complex nature of modern drug research. Invited authors present their biological, chemical, biochemical, physiological, immunological, pharmaceutical, toxicological, pharmacological and clinical expertise in carefully written reviews and provide the newcomer and the specialist alike with an up-to-date comprehensive list of prime references. Each volume of Progress in Drug Research contains fully cross-referencing indices which link the books together, forming a virtually encyclopaedic work. The series thus serves as an important, time-saving source of information for researchers concerned with drug research and all those who need to keep abreast of the many recent developments in the quest for new and better medicines.

Volume 43 of "Progress in Drug Research" contains five reviews and the various indexes which facilitate its use and establish the connection with the previous volumes. The articles in this volume deal with high cholesterol blood levels and other dyslipidemias; search of ideal antihypertensive drugs; the natural PQlyamines and the immune system; biologically active quinazolones and with production and action of interferons. In the 35 years the PDR has existed, the Editor has enjoyed the valuable help and advice of many colleagues. Readers, the authors of the reviews, and last but not least, the reviewers have all contributed greatly to the success of this series. Although the comments received so far have generally been favorable, it is nevertheless necessary to analyze and to reassess the current position and the future direction of such a review series. So far, it has been the Editors intention to help disseminate information on the vast domain of drug research, and to provide the reader with a tool with which to keep abreast of the latest developments and trends. The reviews in PDR are useful to the non-specialist, who can obtain an overview of a particular field of drug research in a relatively short time. The specialist readers of PDR will appreciate the reviews' comprehensive bibliographies, and, in addition, they may even get fresh impulses for their own research. Finally, the readers can use the 43 volumes of PDR as an encyclopedic source of information.

In the treatment of infections caused by rapidly mutating viruses like human immunodeficiency virus (HIV), combination therapy with multiple drugs act ing by different mechanisms offers several advantages over monotherapy. It may provide: synergistic effect, possible reduction of dosages and side-effects, and reduction of the chance of drug resistance. In the past few years, hun dreds of HIV protease inhibitors have been synthesized and tested in order to overcome the limitations of reverse transcriptase inhibitors like zidovudine and others. In this review, emphasis is placed on the development of HIV pro tease inhibitors as antiviral agents against HIY, and structure-activity rela tionship analysis of saquinavir and related compounds. Limitations of some protease inhibitors and ways to overcome the shortcomings are presented. Among these many protease inhibitors five have been marketed during 1995-1999. They are saquinavir, ritonavir, indinavir, nelfinavir and ampre navir. Their different structural features, important physicochemical, phar macokinetic and clinical profiles are presented in a table form for easy com parison. It is hoped that in the future new drugs based on additional mech anisms can be developed for the treatment of AIDS. Contents 4 1 Introduction .................................................................... . HIV protease as a target for chemotherapy ................................... . 2 5 Design of protease inhibitors .................................................. . 3 5 Basis of rational design of HIV protease inhibitors ........................... . 3.1 5 New development of HIV protease inhibitors ................................ . 6 3.2 HIV protease inhibitors on the market ........................................ . 20 4 20 4.1 SAR of saquinavir and related compounds .................................... ."

Founded in 1959 by its current Editor, the series has moved from its initial focus on medicinal chemistry to a much wider scope. Today it encompasses all fields concerned with the development of new therapeutic drugs and the elucidation of their mechanisms of action, reflecting the increasingly complex nature of modern drug research. Invited authors present their biological, chemical, biochemical, physiological, immunological, pharmaceutical, toxicological, pharmacological and clinical expertise in carefully written reviews and provide the newcomer and the specialist alike with an up-to-date comprehensive list of prime references. Each volume of Progress in Drug Research contains fully cross-referencing indices which link the books together, forming a virtually encyclopaedic work. The series thus serves as an important, time-saving source of information for researchers concerned with drug research and all those who need to keep abreast of the many recent developments in the quest for new and better medicines.