Naturally Occurring Benzodiazepines, Endozepines, and their Receptors
Implications for Benzodiazepine Therapy and Withdrawal
Frontiers in Neurotherapeutics Series

Understanding and addressing the current opioid crisis requires knowledge of endogenous opioids (endorphins and enkephalins), but there is now evidence for a benzodiazepine crisis. Are there endogenous benzodiazepine-like substances?and what do they do? How do they affect antianxiety drugs and their adverse effects? Do they explain enigmatic prolonged benzodiazepine withdrawal syndrome? This book raises important questions about the clinical consequences of ignoring the existence of or understanding the potential influence of endogenous benzodiazepines on the therapeutic effect of benzodiazepines, their adverse effects, and the problems of withdrawal from them and other benzodiazepine receptor agonists.

FEATURES

• Discusses endogenous benzodiazepine-like substances?what do they do, and do they affect antianxiety drugs and their adverse effects?
• Presents information on enigmatic prolonged benzodiazepine withdrawal syndrome
• Describes the compounds acting at the BDZ binding sites, both exogenous (classical BDZ drugs and BDZ from food and plants) and endogenous (endozepines)
• Assesses the putative interactions in physiology, pathology, and pharmacology of the compounds acting at the BDZ binding sites

Dr. Raffa is Adjunct Professor at the University of Arizona College of Pharmacy and Professor Emeritus at Temple University School of Pharmacy. He has co-authored or edited several books on pharmacology and thermodynamics, is a co-editor of two journals, is a past president of the Mid-Atlantic Pharmacology Society, and is the recipient of research and teaching awards.

Dr. Amantea is Associate Professor of Pharmacology at the Department of Pharmacy, Health and Nutritional Sciences of the University of Calabria (Italy), where she is the leader of the Stroke Research Unit at the Section of Preclinical and Translational Pharmacology operating in the frame of the Italian Stroke Organization (ISO) Basic Science. She is a member of the Editorial Board and the Guest Editor of the 2016 Neuroscience section of Current Opinion in Pharmacology (Elsevier), and the founder and the editor of the CRC Press Frontiers in Neurotherapeutics series.

1 Introduction 2 Benzodiazepines and Related Substances: Chemistry 3 Central Benzodiazepine Receptors: Structure and Function 4 Benzodiazepines and Related Substances: Therapeutic Uses and Problems 5 Peripheral Benzodiazepine Receptors 6 The search for Endogenous Benzodiazepines in Humans 7 Evidence for Presence in Non-human Animals 8 Biologically Active Phytochemicals Having Benzodiazepine-like Actions 9 Benzodiazepines, Flavonoids and GABA 10 The Microbiome and Benzodiazepines: A Connection? 11 Anxiety, Sleep, and Benzodiazepines 12 The Effects of Benzodiazepines on Memory 13 Naturally Occurring and Exogenous Benzodiazepines in Epilepsy: An Update 14 Impact of Endogenous Benzodiazepines on Tolerance, Abuse, or Withdrawal

Dr. Raffa is Adjunct Professor at the University of Arizona College of Pharmacy and Professor Emeritus at Temple University School of Pharmacy. He earned bachelor’s degrees in Chemical Engineering and in Physiological Psychology (both from the University of Delaware), master’s degrees in Biomedical Engineering (from Drexel University) and Toxicology (Thomas Jefferson University), and a doctorate in Pharmacology (Temple University School of Medicine). He was a Research Fellow and a Team Co-Leader for drug discovery at Johnson & Johnson. He is a cofounder of CaRafe Drug Innovation and Enalare Therapeutics, and is CSO of Neumentum Inc. He is co-holder of several patents and has published more than 350 papers. He has co-authored or edited several books on pharmacology and thermodynamics, is a Co-Editor of two journals, is a past president of the Mid-Atlantic Pharmacology Society and is the recipient of research and teaching awards.

Dr. Amantea is Associate Professor of Pharmacology at the Department of Pharmacy, Health and Nutritional Sciences of the University of Calabria (Italy), where she is the leader of the Stroke Research Unit at the Section of Preclinical and Translational Pharmacology operating in the frame of the Italian Stroke Organization (ISO) Basic Science. She earned a PharmD cum laude from the University of Calabria in 1998 and a PhD in Pharmacology from the University of Birmingham (UK) in 2003. She continued her postdoctoral activity at the Department of Pharmacology of the Medical School of Birmingham University where, under the guidance of Prof. Norman G. Bowery, she worked on the involvement of GABAB receptors in neurological disorders. During her formative years, she was visiting researcher at respected research laboratories of the Universities of Madrid, Lausanne, Florence and Rome. She published more than 60 papers on peer-reviewed journals. She is member of the Editorial Board and Guest Editor of the 2016 Neuroscience sectio