Cholinesterases And Anticholinesterase Agents

Although the anticholinesterase (anti-ChE) agents have only limited applica tions in therapy, and from the viewpoint of practical significance they are more appropriately classified as toxic compounds or insecticides than as drugs, in their capacity of pharmacological tools they have few equals. The concept of neuro humoral transmission was originally established largely from experiments in which physostigmine, or eserine, was employed to protect acetylcholine (ACh), the trans mitter of the cholinergic nerves, from rapid hydrolytic destruction by acetyl cholinesterase (AChE) and other cholinesterases (ChE's). Since then, a great num ber of additional reversible and irreversible anti-ChE agents also have been indis pensable in studies of synaptic and neuroeffector transmission, and of other physiological processes. At the same time, there is practically no other class of compounds for which a mechanism of pharmacological action can be described in such concrete biochemical and physiological terms. Consequently, it is not sur prising that a huge literature has developed on these several closely interdependent topics. The assembling anrl proper correlation of this material for the present volume has taken the collaborative efforts of over two dozen . investigators. It iR believed that their contributions to this end will prove invaluable to future in vestigators in providing a ready, inclusive source of established information, in defining areas where further studies are indicated, and in preventing unnecessary duplication of past work. How well these aims have been accomplished will be for time and the reader to judge.

The Fifth International Meeting on Cholinesterases convened in Madras, India, in September of 1994. The long and rich history and culture of India provided an excellent setting for the meeting. More than 120 delegates from Asia, Australia, Europe and North America heard 54 oral presentations and viewed 54 posters on current research on enzymes of the cholinesterase family. The aim of this book is to compile the presentations of the Fifth International Meeting on Cholinesterases into a volume that describes recent investigations on the structure and catalytic function of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and related enzymes, as well as studies on the molecular and cellular biology of these enzymes and the genes which encode them. Cholinesterases enjoy a long and storied history in diverse areas. In basic biochemical research, AChE is one of the best studied, though yet enigmatic, of enzymes. The efficient catalytic function of this enzyme presents the biochemist with a fundamental challenge in understanding the relationship between structure and function. AChE and BuChE belong to a family of proteins, the alB hydrolase fold family, whose constituents evolutionarily diverged from a common ancestor. Proteins in this family have a wide range of physiological functions. In commerce, AChE is a prime target for agricultural insect control, and for the development of therapeutic agents for Alzheimer's disease.

Human Cholinesterases and Anticholinesterases summarizes the many fundamental concepts of human cholinesterases (ChEs) and their inhibitors. This book is divided into three chapters that represent human cholinesterase research studies from different points of view. Chapter 1 deals with the biochemical and biological background of human ChEs. This chapter also examines the molecular polymorphism, genomic origin, genetic variants, and biological roles of these enzymes. Chapter 2 provides the molecular characterization of human ChE genes and their multileveled regulation, with a special emphasis on butyrylcholinesterase. Chapter 3 discusses the scientific, ecological, and clinical implications of the studies presented in the previous chapters. Protein scientists, engineers, and researchers will find this work invaluable.

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This text/reference book provides the most comprehensive coverage of anticholinesterase compounds (Organophosphates and Carbamates), which constitute the largest number of chemicals that are primarily used as insecticides in agriculture, industry, and around the home/garden. Some OPs (nerve agents) have been used in chemical warfare and terrorist attacks, while some OPs and CMs have been recommended as therapeutic agents in human medicine as well as in veterinary medicine. Many chemicals of both classes are extremely toxic and lack selectivity, thus their inadvertent/accidental use continues to pose a threat to human and animal health, aquatic systems and wildlife. These anticholinesterase agents produce a variety of toxicological effects in target and nontarget organs. In light of this complexicity, this multi-authored book is written by the well known scientists from many countries. The book is organized into nine sections, with a total of 49 chapters, to provide in-depth knowledge on various aspects of OP and CM compounds, including their use, classification, mechanism-based toxicity, and prophylactic and therapeutic measurements. Several chapters are written with special emphasis to cover timely topics, such as chemical warfare agents, physiologically-based pharmacokinetic modeling, structure and function of cholinesterases, paraoxonase, carboxylesterases; developmental neurotoxicity, the intermediate syndrome, oxidative stress, endocrine disruption, and DNA damage/gene expression and carcinogenesis. Section-VI with 5 chapters is specifically devoted to risk assessment, and safety and regulatory guidelines for pesticides. Describes everything you need to know about Organophosphates and Carbamates Extensively covers pesticides, nerve agents, therapeutic drugs, and flame retardants Describes epidemiology of the world's major disasters involving Organophosphates and Carbamates Covers animal, human, aquatic, and wildlife toxicity of Anticholinesterases Insights into in-depth cholinergic and noncholinergic mechanisms of toxicity Describes recent advancements in cholinesterases, paraoxonases, carboxylesterases, oxidative stress, endocrine disruption, cardiac and pulmonary toxicity, and carcinogenesis Provides in vitro and in vivo models for neurotoxicity testing Integrates knowledge of studies in lab animals and humans Offers risk/safety assessment and national/international guidelines for permissible levels of pesticide residues Describes management of Anticholinesterase poisoning in humans