Defined by ASPET as the study of the effects of chemical agents of therapeutic value or with the potential toxicity on biological systems, pharmacology is critical to understanding how drugs can correct the biochemical abnormalities responsible for human illness. It is one of the core disciplines students need to master in order to develop effective drugs and therapeutics.
This book, the updated and enhanced English translation of a successful and multi–edition Italian text, covers basic and general pharmacology, from a cellular and molecular perspective, with particular attention mechanisms of drug action the fundamental basis for proper clinical use – without neglecting drug interactions, general physiological functions, and the toxicological effects of chemical compounds . As opposed to classical pharmacology textbooks, which spend more time detailing medical and therapeutic effects, the authors offer thorough discussion of drug action mechanisms at cell and molecular level and the rules governing drug pharmacokinetics and development.
The target–oriented approach within the text changes the common perception of drugs as chemical entities affecting organisms and highlights the interdisciplinary and dynamic nature of pharmacological research. As such, the book introduces pharmacologists to a more integrated view of their discipline and fosters a holistic approach to the analysis and treatment of diseases one in which drugs are regarded as critical tools to discover new cell functions, mechanisms, and therapies.
Complementary to the main text, the book has a companion website that builds on the content within the book itself by addressing more specific subjects and methodologies. The site is ideal for readers who have mastered the basic principles and are seeking more in–depth knowledge of detailed topics.
More than just a course text for pharmacology students, this book can also be a key reference and resource for researchers and professionals involved in any aspect of drug development
LIST OF CONTRIBUTORS xlvi
SECTION 1 INTRODUCTION TO PHARMACOLOGY 1
1 Essential Lexicon of Pharmacology 3Francesco Clementi and Guido Fumagalli2 A Short History of Pharmacology 8Vittorio A. SironiSECTION 2 GETTING THE DRUG TO ITS SITE OF ACTION 19
3 Cellular Basis of Pharmacokinetics 21Riccardo Fesce and Guido Fumagalli4 Drug Absorption and Administration Routes 31Riccardo Fesce and Guido Fumagalli5 Drug Distribution and Elimination 45Riccardo Fesce and Guido Fumagalli6 Drug Metabolism 61Enzo Chiesara Laura Marabini and Sonia Radice Metabolic Modification of Drug Activity 7 Control of Drug Plasma Concentration 73Riccardo Fesce and Guido FumagalliSECTION 3 RECEPTORS AND SIGNAL TRANSDUCTION 91
8 Drug Receptor Interactions: Quantitative and Qualitative Aspects 93Gian Enrico Rovati and Valérie Capra9 Receptors and Modulation of Their Response 109Francesco Clementi and Guido Fumagalli10 A daptation to Drug Response and Drug Dependence 121Cristiano Chiamulera11 Pharmacological Modulation of Posttranslational Modifications 130Monica Di Luca Flavia Valtorta and Fabrizio Gardoni12 Calcium Homeostasis Within the Cells 139Jacopo Meldolesi and Guido Fumagalli13 Pharmacology of Map Kinases 147Lucia Vicentini and Maria Grazia Cattaneo14 Small G Proteins 154Erzsébet Ligeti and Thomas Wieland15 Integration in Intracellular Transduction of Receptor Signals 166Jacopo MeldolesiSECTION 4 RECEPTOR CLASSES 173
16 Ligand–Gated Ion Channels 175Cecilia Gotti and Francesco Clementi17 G–Protein–Coupled Receptors 189Lucia Vallar Maria Pia Abbracchio and Lucia Vicentini18 Growth Factor Receptors 202Silvia Giordano Carla Boccaccio and Paolo M. Comoglio19 Cytokine Receptors 217Massimo Locati20 A dhesion Molecule Receptors 225Giorgio Berton and Carlo Laudanna21 Soluble Cytokine Receptors and Monoclonal Antibodies in Pathophysiology and Therapy 235Alberto Mantovani and Annunciata VecchiSECTION 5 MODULATION OF GENE ESPRESSION 241
22 Pharmacology of Transcription 243Roberta Benfante and Diego Fornasari23 Pharmacogenetics and Personalized Therapy 256Diego Fornasari24 Intracellular Receptors 268Adriana Maggi and Elisabetta Vegeto25 Rna Molecule as a Drug: From Rna Interference to Aptamers 284Valerio Fulci and Giuseppe MacinoSECTION 6 REGENERATIVE MEDICINE 293
26 Regenerative Medicine and Gene Therapy 295Luciano Conti and Elena CattaneoSECTION 7 PHARMACOLOGICAL CONTROL OF MEMBRANE TRANSPORT 309
27 Ion Channels 311Maurizio Taglialatela and Enzo Wanke28 Membrane Transporters 345Lucio Annunziato Giuseppe Pignataro and Gianfranco Di Renzo29 Neurotransmitter Transporters 359Gaetano Di ChiaraSECTION 8 CONTROL OF PROTEOLYSIS 377
30 Intracellular Proteolysis 379Fabio Di Lisa and Edon Melloni31 Extracellular Proteolysis 395Francesco BlasiSECTION 9 CONTROL OF CELL CYCLE AND CELLULAR PROLIFERATION 403
32 Cell Cycle and Cell Death 405Marco Corazzari and Mauro Piacentini33 Mechanisms of Action of Antitumor Drugs 415Giovanni Luca Beretta Laura Gatti and Paola PeregoSECTION 10 CONTROL OF CELLULAR METABOLISM 431
34 Mitochondria Oxidative Stress and Cell Damage: Pharmacological Perspectives 433Clara De Palma Orazio Cantoni and Fabio Di Lisa35 Pharmacological Control of Lipid Synthesis 439Lorenzo Arnaboldi Alberto Corsini and Nicola Ferri36 Glucose Transport and Pharmacological Control of Glucose Metabolism 452Paolo Moghetti and Giacomo ZoppiniSECTION 11 INTERCELLULAR COMMUNICATION 463
37 Pharmacological Regulation of Synaptic Function 465Michela Matteoli Elisabetta Menna Costanza Capuano and Claudia Verderio38 Catecholaminergic Transmission 477Pier Franco Spano Maurizio Memo M. Cristina Missale Marina Pizzi and Sandra Sigala39 Cholinergic Transmission 496Giancarlo Pepeu40 The Serotonergic Transmission 509Maurizio Popoli Laura Musazzi and Giorgio Racagni41 Histaminergic Transmission 520Emanuela Masini and Laura Lucarini42 Gabaergic Transmission 529Mariangela Serra Enrico Sanna and Giovanni Biggio43 Glutamate–Mediated Neurotransmission 541Flavio Moroni44 Purinergic Transmission 553Stefania Ceruti Flaminio Cattabeni and Maria Pia Abbracchio45 Neuropeptides 565Lucia Negri and Roberta Lattanzi46 The Opioid System 572Patrizia Romualdi and Sanzio Candeletti47 The Endocannabinoid System 585Daniela Parolaro and Tiziana Rubino48 Pharmacology of Nitric Oxide 596Emilio Clementi49 A rachidonic Acid Metabolism 608Carlo Patrono and Paola PatrignaniSECTION 12 PHARMACOLOGY OF DEFENCE PROCESSES 623
50 Pharmacological Modulation of the Immune System 625Carlo Riccardi and Graziella Migliorati51 Mechanism of Action of Anti–Infective Drugs 641Francesco ScaglioneSECTION 13 TOXICOLOGY AND DRUG INTERACTIONS 663
52 Introduction to Toxicology 665Helmut Greim53 Drug Interactions 678Achille P. Caputi Giuseppina Fava and Angela De SarroSECTION 14 DRUG DEVELOPMENT 687
54 Preclinical Research and Development of New Drugs 689Ennio Ongini55 Role of Drug Metabolism and Pharmacokinetics in Drug Development 700Simone Braggio and Mario Pellegatti56 Clinical Development of a New Drug and Methodology of Drug Trials 708Carlo PatronoIndex 714
Francesco Clementi is a Professor Emeritus of Pharmacology at the University of Milan. He has been President of several national and international societies and is member of the Accademia dei Lincei, the prestigious Academy of Italian Sciences. He authored over 200 publications dealing with neurotransmitter receptors and co–edited several books on neuropharmacology and cell biology including all four editions of the Italian language version of this book, Farmacologia Generale e Molecolare.
Guido Fumagalli has been the Dean of Faculty Director of the PhD School of Translational Medicine, Vice–Provost for Research, and Vice–Provost for International Affairs at the University of Verona. He has over 80 publications in international journals to his credit along with numerous books on pharmacology and sports science