title: Activation of the γ-Aminobutyric Acid Type B (GABA(B)) Receptor by Agonists and Positive Allosteric Modulators.
abstract: Since the discovery of the GABA(B) agonist and muscle relaxant baclofen, there have been substantial advancements in the development of compounds that activate the GABA(B) receptor as agonists or positive allosteric modulators. For the agonists, most of the existing structure-activity data apply to understanding the role of substituents on the backbone of GABA as well as replacing the carboxylic acid and amine groups. In the cases of the positive allosteric modulators, the allosteric binding site(s) and structure-activity relationships are less well-defined; however, multiple classes of molecules have been discovered. The recent report of the X-ray structure of the GABA(B) receptor with bound agonists and antagonists provides new insights for the development of compounds that bind the orthosteric site of this receptor. From a therapeutic perspective, these data have enabled efforts in drug discovery in areas of addiction-related behavior, the treatment of anxiety, and the control of muscle contractility.
authors: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University , West Lafayette, Indiana 47907, United States.
authors: Katie M
authors: KM
authors: Brown
authors: Department of Biomolecular Sciences, University of Mississippi , University, Mississippi 38677, United States.
authors: Kuldeep K
authors: KK
authors: Roy
authors: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University , West Lafayette, Indiana 47907, United States.
authors: Gregory H
authors: GH
authors: Hockerman
authors: Department of Biomolecular Sciences, University of Mississippi , University, Mississippi 38677, United States.
authors: Robert J
authors: RJ
authors: Doerksen
authors: Department of Biomolecular Sciences, University of Mississippi , University, Mississippi 38677, United States.
authors: David A
authors: DA
authors: Colby
mesh_terms: D000818:Animals; D018755:GABA Agonists / Q000737:chemistry / Q000494:pharmacology*; D018756:GABA Antagonists / Q000737:chemistry / Q000494:pharmacology; D018757:GABA Modulators / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D008968:Molecular Conformation; D018080:Receptors, GABA-B / Q000737:chemistry / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D018755:GABA Agonists; D018756:GABA Antagonists; D018757:GABA Modulators; D018080:Receptors, GABA-B