The complexity of the GABAA receptor shapes unique pharmacological profiles

• Published in: Drug discovery today Vol. 14; no. 17-18; pp. 866 - 875
• Main Authors: D'HULST, Charlotte, ATACK, John R, KOOY, R. Frank
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier 01.09.2009
• Subjects: Animals; Benzodiazepines - pharmacology; Binding Sites - drug effects; Biological and medical sciences; Brain - metabolism; Drug Delivery Systems; Drug Discovery; gamma-Aminobutyric Acid - metabolism; General pharmacology; Humans; Medical sciences; Mice; Mice, Transgenic; Models, Biological; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Receptors, GABA-A - chemistry; Receptors, GABA-A - drug effects; Receptors, GABA-A - genetics; Receptors, GABA-A - metabolism; Shape; Pharmaceutical technology; Gabaergic receptor A; Complexity
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2009.06.009

Gamma-amino butyric acid (GABA) is the most abundant inhibitory neurotransmitter in the central nervous system (CNS) and many physiological actions are modulated by GABA(A) receptors. These chloride channels can be opened by GABA and are a target for a variety of important drugs such as benzodiazepines, barbiturates, neuroactive steroids, convulsants and anaesthetics. GABA(A) receptors are involved in anxiety, feeding and drinking behaviour, circadian rhythm, cognition, vigilance, and learning and memory. Moreover, deficits in the functional expression of GABA(A) receptors have been implicated in multiple neurological and psychiatric diseases. This review aims to discuss the unique physiological and pharmacological properties of the multitude of GABA(A) receptor subtypes present in the CNS, making this receptor an important target for novel rational drug therapy.