Anxiolytic β-Carbolines: From Molecular Biology to the Clinic

ISBN-13: 9783642784538 / Angielski / Miękka / 2011 / 151 str.

David N. Stephens

Opis

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.

Spis treści

Discovery of ?-Carboline Ligands for Benzodiazepine Receptors.- ?-Carboline-3-Carboxylic Acid Ethyl Ester: A Lead for New Psychotropic Drugs.- Molecular Biology of Gamma-Aminobutyric Acid Type A/Benzodiazepine Receptors.- Immunohistochemical Mapping of Gamma-Aminobutyric Acid Type A Receptor Alpha Subunits in Rat Central Nervous System.- Abecarnil is a Full Agonist at Some and a Partial Agonist at Other Recombinant Gamma-Aminobutyric Acid Type A Receptor Subtypes.- Pharmacological Evidence for Full Agonist Activity of Abecarnil at Certain Receptors.- Abecarnil: A Novel Anxiolytic with Mixed Full Agonist/Partial Agonist Properties in Animal Models of Anxiety and Sedation.- Abecarnil Shows Reduced Tolerance Development and Dependence Potential in Comparison to Diazepam.- Behavioral Pharmacology of Abecarnil in Baboons: Reduced Dependence and Abuse Potential.- Abecarnil Used to Treat Benzodiazepine Withdrawal.- Abecarnil, A New ?-Carboline Anxiolytic: Preliminary Clinical Pharmacology.