TY - CHAP
T1 - Astrocytic GABA Transporters
T2 - Pharmacological Properties and Targets for Antiepileptic Drugs
AU - Schousboe, Arne
AU - Wellendorph, Petrine
AU - Frølund, Bente
AU - Clausen, Rasmus P
AU - Krogsgaard-Larsen, Povl
PY - 2017
Y1 - 2017
N2 - Inactivation of GABA-mediated neurotransmission is achieved by high-affinity transporters located at both GABAergic neurons and the surrounding astrocytes. Early studies of the pharmacological properties of neuronal and glial GABA transporters suggested that different types of transporters might be expressed in the two cell types, and such a scenario was confirmed by the cloning of four distinctly different GABA transporters from a number of different species. These GABA-transport entities have been extensively characterized using a large number of GABA analogues of restricted conformation, and several of these compounds have been shown to exhibit pronounced anticonvulsant activity in a variety of animal seizure models. As proof of concept of the validity of this drug development approach, one GABA-transport inhibitor, tiagabine, has been developed as a clinically active antiepileptic drug. This review provides a detailed account of efforts to design new subtype-selective GABA-transport inhibitors aiming at identifying novel antiepileptic drug candidates.
AB - Inactivation of GABA-mediated neurotransmission is achieved by high-affinity transporters located at both GABAergic neurons and the surrounding astrocytes. Early studies of the pharmacological properties of neuronal and glial GABA transporters suggested that different types of transporters might be expressed in the two cell types, and such a scenario was confirmed by the cloning of four distinctly different GABA transporters from a number of different species. These GABA-transport entities have been extensively characterized using a large number of GABA analogues of restricted conformation, and several of these compounds have been shown to exhibit pronounced anticonvulsant activity in a variety of animal seizure models. As proof of concept of the validity of this drug development approach, one GABA-transport inhibitor, tiagabine, has been developed as a clinically active antiepileptic drug. This review provides a detailed account of efforts to design new subtype-selective GABA-transport inhibitors aiming at identifying novel antiepileptic drug candidates.
KW - Journal Article
U2 - 10.1007/978-3-319-55769-4_14
DO - 10.1007/978-3-319-55769-4_14
M3 - Book chapter
C2 - 28828616
VL - 16
T3 - Advances in Neurobiology
SP - 283
EP - 296
BT - Glial Amino Acid Transporters
PB - Springer
ER -