Premium
The effect of two lipophilic γ‐aminobutyric acid uptake blockers in CA1 of the rat hippocampal slice
Author(s) -
Rekling Jens C.,
Jahnsen Henrik,
Laursen Arne Mosfeldt
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb14661.x
Subject(s) - inhibitory postsynaptic potential , nipecotic acid , gabaa receptor , pharmacology , gamma aminobutyric acid , neurotransmission , hippocampal formation , chemistry , aminobutyric acid , neuroscience , slice preparation , bicuculline , neurotransmitter , central nervous system , biology , biochemistry , receptor
1 Drugs that increase inhibitory synaptic transmission in the central nervous system may be valuable tools in the treatment of seizures. Theoretically, substances that block the uptake of inhibitory transmitters such as γ‐aminobutyric acid (GABA) into intracellular compartments should also increase inhibition and therefore have potential value as antiepileptic drugs. However, most of these substances penetrate the blood‐brain barrier poorly and have therefore until now had limited value. NO‐05–0328 and NO‐05–0329 are two new lipophilic GABA uptake inhibitors that readily enter the CNS from the blood. 2 We have investigated the effect of these two uptake inhibitors on the responses to exogenous GABA and on GABA‐mediated inhibitory synaptic potentials in pyramidal neurones of the CA1 region in the rat hippocampal slice. 3 We found that both drugs increased the amplitude and duration of responses to exogenous GABA. Furthermore, the inhibitory synaptic potentials increased in amplitude. This increase was seen in both early and late phases of the synaptic potentials. We conclude that NO‐05–0328 and NO‐05–0329, at least in vitro , are more effective than older GABA uptake inhibitors such as nipecotic acid and they therefore deserve consideration for clinical use.