Inhibitory effects of quinolone antibacterial agents on gamma-aminobutyric acid binding to receptor sites in rat brain membranes.
The specific binding of 3H-labeled gamma-aminobutyric acid ([3H]GABA) to synaptic plasma membranes from rat brains was inhibited by various quinolonecarboxylic acid derivatives (quinolones), and these inhibitions were concentration dependent. The binding of [3H]muscimol to GABAA sites was also inhibited. These inhibitory potencies differed widely among the quinolones examined. The Dixon plots showed that a newly developed difluorinated quinolone, NY-198 [1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3- quinolinecarboxylic acid hydrochloride], competitively inhibits the receptor bindings of [3H]GABA and [3H]muscimol. In conclusion, our findings suggest that the inhibition of GABA binding to receptors (including uptake sites) in the brain may be involved in the induction of epileptogenic neurotoxicities by quinolones.
Tsuji
A
A
Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Sato
H
H
Kume
Y
Y
Tamai
I
I
Okezaki
E
E
Nagata
O
O
Kato
H
H
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D009118:Muscimol / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000890:Anti-Infective Agents; D011804:Quinolines; D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid