With a focus on functional relationships between drugs and their targets, this book covers basic and general pharmacology, from a cellular and molecular perspective, with particular attention  to the mechanisms of drug action – the fundamental basis for proper clinical use- without neglecting clinical application, toxicology and pharmacokinetics.

•    Covers cell and molecular pharmacology, bringing together current research on regulation of drug targets, at a level appropriate for advanced undergrad and graduate students
•    Discusses the relevance of pharmacokinetics and drug development for the clinical application of drugs
•    Presents material from the perspective of drug targets and interaction, the theoretical basis of drug action analysis, and drug properties
•    Focuses on structure-function relationships of drug targets – informing about their biochemical and physiologic functions and experimental and clinical pathways for drug discovery and development
•    Has a companion website that offers a host of resources: short additional chapters about methodology, topics at the forefront of research, all figures and tables from the book, and Power Point slides

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

LIST OF CONTRIBUTORS xlvi

Preface xlix

SECTION 1 INTRODUCTION TO PHARMACOLOGY 1

1 Essential Lexicon of Pharmacology 3
Francesco Clementi and Guido Fumagalli

2 A Short History of Pharmacology 8
Vittorio A. Sironi

SECTION 2 GETTING THE DRUG TO ITS SITE OF ACTION 19

3 Cellular Basis of Pharmacokinetics 21
Riccardo Fesce and Guido Fumagalli

4 Drug Absorption and Administration Routes 31
Riccardo Fesce and Guido Fumagalli

5 Drug Distribution and Elimination 45
Riccardo Fesce and Guido Fumagalli

6 Drug Metabolism 61
Enzo Chiesara Laura Marabini and Sonia Radice Metabolic Modification of Drug Activity

7 Control of Drug Plasma Concentration 73
Riccardo Fesce and Guido Fumagalli

SECTION 3 RECEPTORS AND SIGNAL TRANSDUCTION 91

8 Drug–Receptor Interactions: Quantitative and Qualitative Aspects 93
Gian Enrico Rovati and Valérie Capra

9 Receptors and Modulation of Their Response 109
Francesco Clementi and Guido Fumagalli

10 A daptation to Drug Response and Drug Dependence 121
Cristiano Chiamulera

11 Pharmacological Modulation of Posttranslational Modifications 130
Monica Di Luca Flavia Valtorta and Fabrizio Gardoni

12 Calcium Homeostasis Within the Cells 139
Jacopo Meldolesi and Guido Fumagalli

13 Pharmacology of Map Kinases 147
Lucia Vicentini and Maria Grazia Cattaneo

14 Small G Proteins 154
Erzsébet Ligeti and Thomas Wieland

15 Integration in Intracellular Transduction of Receptor Signals 166
Jacopo Meldolesi

SECTION 4 RECEPTOR CLASSES 173

16 Ligand-Gated Ion Channels 175
Cecilia Gotti and Francesco Clementi

17 G-Protein-Coupled Receptors 189
Lucia Vallar Maria Pia Abbracchio and Lucia Vicentini

18 Growth Factor Receptors 202
Silvia Giordano Carla Boccaccio and Paolo M. Comoglio

19 Cytokine Receptors 217
Massimo Locati

20 A dhesion Molecule Receptors 225
Giorgio Berton and Carlo Laudanna

21 Soluble Cytokine Receptors and Monoclonal Antibodies in Pathophysiology and Therapy 235
Alberto Mantovani and Annunciata Vecchi

SECTION 5 MODULATION OF GENE ESPRESSION 241

22 Pharmacology of Transcription 243
Roberta Benfante and Diego Fornasari

23 Pharmacogenetics and Personalized Therapy 256
Diego Fornasari

24 Intracellular Receptors 268
Adriana Maggi and Elisabetta Vegeto

25 Rna Molecule as a Drug: From Rna Interference to Aptamers 284
Valerio Fulci and Giuseppe Macino

SECTION 6 REGENERATIVE MEDICINE 293

26 Regenerative Medicine and Gene Therapy 295
Luciano Conti and Elena Cattaneo

SECTION 7 PHARMACOLOGICAL CONTROL OF MEMBRANE TRANSPORT 309

27 Ion Channels 311
Maurizio Taglialatela and Enzo Wanke

28 Membrane Transporters 345
Lucio Annunziato Giuseppe Pignataro and Gianfranco Di Renzo

29 Neurotransmitter Transporters 359
Gaetano Di Chiara

SECTION 8 CONTROL OF PROTEOLYSIS 377

30 Intracellular Proteolysis 379
Fabio Di Lisa and Edon Melloni

31 Extracellular Proteolysis 395
Francesco Blasi

SECTION 9 CONTROL OF CELL CYCLE AND CELLULAR PROLIFERATION 403

32 Cell Cycle and Cell Death 405
Marco Corazzari and Mauro Piacentini

33 Mechanisms of Action of Antitumor Drugs 415
Giovanni Luca Beretta Laura Gatti and Paola Perego

SECTION 10 CONTROL OF CELLULAR METABOLISM 431

34 Mitochondria Oxidative Stress and Cell Damage: Pharmacological Perspectives 433
Clara De Palma Orazio Cantoni and Fabio Di Lisa

35 Pharmacological Control of Lipid Synthesis 439
Lorenzo Arnaboldi Alberto Corsini and Nicola Ferri

36 Glucose Transport and Pharmacological Control of Glucose Metabolism 452
Paolo Moghetti and Giacomo Zoppini

SECTION 11 INTERCELLULAR COMMUNICATION 463

37 Pharmacological Regulation of Synaptic Function 465
Michela Matteoli Elisabetta Menna Costanza Capuano and Claudia Verderio

38 Catecholaminergic Transmission 477
Pier Franco Spano Maurizio Memo M. Cristina Missale Marina Pizzi and Sandra Sigala

39 Cholinergic Transmission 496
Giancarlo Pepeu

40 The Serotonergic Transmission 509
Maurizio Popoli Laura Musazzi and Giorgio Racagni

41 Histaminergic Transmission 520
Emanuela Masini and Laura Lucarini

42 Gabaergic Transmission 529
Mariangela Serra Enrico Sanna and Giovanni Biggio

43 Glutamate-Mediated Neurotransmission 541
Flavio Moroni

44 Purinergic Transmission 553
Stefania Ceruti Flaminio Cattabeni and Maria Pia Abbracchio

45 Neuropeptides 565
Lucia Negri and Roberta Lattanzi

46 The Opioid System 572
Patrizia Romualdi and Sanzio Candeletti

47 The Endocannabinoid System 585
Daniela Parolaro and Tiziana Rubino

48 Pharmacology of Nitric Oxide 596
Emilio Clementi

49 A rachidonic Acid Metabolism 608
Carlo Patrono and Paola Patrignani

SECTION 12 PHARMACOLOGY OF DEFENCE PROCESSES 623

50 Pharmacological Modulation of the Immune System 625
Carlo Riccardi and Graziella Migliorati

51 Mechanism of Action of Anti-Infective Drugs 641
Francesco Scaglione

SECTION 13 TOXICOLOGY AND DRUG INTERACTIONS 663

52 Introduction to Toxicology 665
Helmut Greim

53 Drug Interactions 678
Achille P. Caputi Giuseppina Fava and Angela De Sarro

SECTION 14 DRUG DEVELOPMENT 687

54 Preclinical Research and Development of New Drugs 689
Ennio Ongini

55 Role of Drug Metabolism and Pharmacokinetics in Drug Development 700
Simone Braggio and Mario Pellegatti

56 Clinical Development of a New Drug and Methodology of Drug Trials 708
Carlo Patrono

Index 714