This book is being published at a time when opioid receptors have recently been cloned. The structural characteristics of opioid receptors and the recent advances in their molecular cloning and expression are explicated. Connecting these cloned opioid receptors with the pharmacology of opioid receptor actions is of particular importance. The use of antisense oligodeoxynucleotides to opioid receptors to elucidate the neural mechanisms of opioid action is detailed. As analgesia is one of the most important clinical functions for opioids and opioid peptides, this book concentrates on the detailed mechanisms of action of opioids and opioid peptides for the production of analgesia. The significant pharmacologic actions of opioids and opioid peptides in gastrointestinal function, immune function, cardiovascular and respiratory regulation, addiction and the cellular mechanisms involved in tolerance and dependence of opioids are also described. The book will be of interest both to researchers investigating the neural mechanisms of the pharmacologic and physiologic functions of the endogenous opioid system and to clinicians who are involved in pain management and assessment.

"This monograph is based upon papers and discussion from the technical review on the medicinal chemistry and molecular pharmacology of opioid peptides and the opiates which took place on September 4-6, 1984, at Bethesda, Maryland. The meeting was sponsored by the Office of Science and the Division of Preclinical Research, National Institute on Drug Abuse. The papers on molecular pharmacology, biosynthesis, and analysis of opioid peptides are presented in this volume. Those on the medical chemistry of opioid peptides appear in NIDA Research Monograph 69" [entitled Opioid peptides : medicinal chemistry] -- page iv.

This pocketbook summarizes the recent developments in this important and controversial aspect of pain management, looking at the benefits and adverse effects of opioids in non-cancer pain.

The interest in opioids such as morphine, the prototypical opioid ligand, has been maintained through the years. The identification of endogenous opioids and their receptors (mu, delta, kappa, and nociceptin), molecular cloning, and the elucidation of the crystal structures of opioid receptors represent key milestones in opioid research. The opioid system modulates numerous pharmacological responses, with therapeutic (i.e., analgesia) and detrimental side effects (i.e., addiction). The medical use and misuse of opioids have dramatically increased, leading to the 21st century opioid crisis. This book presents recent developments in opioid drug discovery, specifically in the medicinal chemistry and pharmacology of new ligands targeting the opioid receptors as effective and safe therapeutics for human diseases. Furthermore, it draws a special attention to advancing concepts and strategies in opioid drug discovery to mitigate opioid liabilities. The diversity among the discussed topics is a testimony to the complexity of the opioid system, which results from the expression, regulation, and functional role of ligands and receptors. The array of multidisciplinary research areas illustrates the rapidly developing basic research and translational activities in opioid drug discovery. This book will serve as a useful reference while also stimulating continued research in the chemistry and pharmacology of opioids and their receptors, with the prospect of developing improved therapies for human diseases, but also improving health and quality of life in general.

Opioid Peptides in Substance Abuse presents an encyclopedic survey of in vivo data examining the interrelationship between endogenous opioids and substance abuse. It emphasizes two main groups of abused substances (morphine congeners and psychostimulants) and addresses the following questions:

The rapidly burgeoning research of the past two decades on agonist-antagonist analgesics and opioid receptors makes this exhaustive review of opioid anal gesics particularly relevant and timely. After an introductory chapter the additional 12 chapters begin logically with morphine and congeners (4- epoxymorphinans) and end with opioid receptors. All principal chemical types of centrally acting analgesics (including endogenous opioid-like substances) and their antagonists as well as the mixed agonist-antagonists are treated thoroughly, although not always (and for good reason) in historical (chrono logical) order. A chapter on miscellaneous types (atypical structures for the most part) includes the benzimidazoles (etonitazene), aminotetralins (dezocine), tetrahydroisoquinolines (methopholine), and so on. Important aspects and correlations of chemistry, pharmacology, and biochemistry are discussed in depth. Literature citations are numerous. For educators, practicing laboratory scientists, and physicians, this scholarly review by two authors well of opioid analgesics versed in the chemistry, pharmacology, and biochemistry will be informative, stimulating, and thought-provoking. Everette L. May Medical College of Virginia Richmond, VA 23298 v Preface The history of opium predates the written word, although knowledge of its constituents dates back less than 200 years. Over the centuries its popularity for the relief of pain has waxed and waned, until today the opiates are widely recognized as excellent analgesics but with disadvantages that have impaired their use seriously. There is a clear need for a potent analgesic with minimal effects on the respiratory centers and gastrointestinal tract and preferably devoid of dependence liability.