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Heterocyclic GABA analogues as new selective inhibitors of astroglial GABA transport
Author(s) -
Schousboe A.,
Larsson O. M.,
Hertz L.,
KrogsgaardLarsen P.
Publication year - 1981
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430010204
Subject(s) - chemistry , in vivo , gabaa receptor , anticonvulsant , pharmacology , biochemistry , gamma aminobutyric acid , receptor , neuroscience , epilepsy , biology , microbiology and biotechnology
A series of heterocyclic GABA analogues were tested as inhibitors of neuronal and glial GABA transport and GABA‐receptor binding. Four compounds were shown to be selective inhibitors of glial GABA uptake, and the inhibition was in each case of the competitive type. The compounds are: β‐proline, homonipecotic acid, and the bicyclic isoxazoles THPO and THAO, the K j values for the glial uptake of these compounds were 400, 700, 550, and 600 μM, respectively. The two latter compounds may be putative anticonvulsant drugs since they are likely to cross the blood‐brain barrier, and since they almost exclusively interfere with glial GABA uptake, which presumably would lead to increased synaptic GABA levels in vivo.