Interaction of various non-steroidal anti-inflammatories and quinolone antimicrobials on GABA response in rat dissociated hippocampal pyramidal neurons.
Interaction of various non-steroidal anti-inflammatory drugs (NSAIDs) and quinolone antimicrobials with gamma-aminobutyric acid (GABA)A receptor-Cl- channel complex was investigated in rat dissociated hippocampal CA1 neurons by using whole-cell mode patch-clamp technique. Neither NSAIDs nor quinolones alone affected the GABA-induced chloride current (ICl). In the presence of norfloxacin (NFLX), one of quinolones, some NSAIDs suppressed the GABA response in a concentration-dependent manner. The inhibitory potency of NSAIDs was 4-biphenylacetic acid (BPA), a metabolite of fenbufen much greater than indomethacin = naproxen greater than mefenamic acid greater than diclofenac greater than piroxicam. The results suggest that fenbufen, indomethacin and naproxen in the presence of quinolones may induce the epileptogenic neurotoxicities via pharmacological interaction with GABAA receptor.
Shirasaki
T
T
Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan.
Harata
N
N
Nakaye
T
T
Akaike
N
N
D042462:4-Quinolones; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*
D042462:4-Quinolones; D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D011963:Receptors, GABA-A