Anxiolytic β-Carbolines: From Molecular Biology to the Clinic (Psychopharmacology Series, 11)

Since the discovery some 15 years ago of benzodiazepine modulatory sites associated with GABA A receptors, great effort has gone into understanding their molecular pharmacology and into developing new anxiolytic drugs that interact selectively with them. Prominent in this research has beenthe discovery that ~-carbolines, a different chemical class from benzodiazepines, also act at these receptors but that their effects are sometimes quite different from those of the benzodiazepines.This book documents the latest discoveries in the molecular biology of the GABA A receptor and reveals how an integration of the results of research inmolecular biology, synthetic chemistry, biochemical and behavioral pharmacology, and clinical pharmacology has paved the way forthe development of ~-carbolines from substances inducing anxiety and convulsions to a novel therapy for anxiety states, achieving a behavioral selectivity through selective actions at subtypes of receptors. Front Matter....Pages I-XI Discovery of β-Carboline Ligands for Benzodiazepine Receptors....Pages 1-6 β-Carboline-3-Carboxylic Acid Ethyl Ester: a Lead for New Psychotropic Drugs....Pages 7-15 Molecular Biology of Gamma-Aminobutyric Acid Type A/Benzodiazepine Receptors....Pages 16-28 Immunohistochemical Mapping of Gamma-Aminobutyric Acid Type-A Receptor Alpha Subunits in Rat Central Nervous System....Pages 29-49 Abecarnil is a Full Agonist at Some, and a Partial Agonist at Other Recombinant GABA A Receptor Subtypes....Pages 50-61 Pharmacological Evidence for Full Agonist Activity of Abecarnil at Certain GABA A Receptors....Pages 62-78 Abecarnil: A Novel Anxiolytic with Mixed Full Agonist/Partial Agonist Properties in Animal Models of Anxiety and Sedation....Pages 79-95 Abecarnil Shows Reduced Tolerance Development and Dependence Potential in Comparison to Diazepam: Animal Studies....Pages 96-112 Behavioral Pharmacology of Abecarnil in Baboons: Reduced Dependence and Abuse Potential....Pages 113-120 Abecarnil Used to Treat Benzodiazepine Withdrawal....Pages 121-131 Abecarnil: A New ß-Carboline Anxiolytic Preliminary Clinical Pharmacology....Pages 132-147 Back Matter....Pages 149-151 Since the discovery some 15 years ago of benzodiazepine modulatory sites associated with GABA A receptors, great effort has gone into understanding their molecular pharmacology and into developing new anxiolytic drugs that interact selectively with them. Prominent in this research has beenthe discovery that ~-carbolines, a different chemical class from benzodiazepines, also act at these receptors but that their effects are sometimes quite different from those of the benzodiazepines. This book documents the latest discoveries in the molecular biology of the GABA A receptor and reveals how an integration of the results of research inmolecular biology, synthetic chemistry, biochemical and behavioral pharmacology, and clinical pharmacology has paved the way forthe development of ~-carbolines from substances inducing anxiety and convulsions to a novel therapy for anxiety states, achieving a behavioral selectivity through selective actions at subtypes of receptors