Celecoxib does not induce convulsions nor does it affect GABAA receptor binding activity in the presence of new quinolones in mice.
We sought to determine whether celecoxib would induce convulsions when coadministered with new quinolone antimicrobial agents in mice. The oral administration of celecoxib (500 mg/kg) alone or in combination with enoxacin (500 mg/kg), lomefloxacin (1000 mg/kg), ciprofloxacin (1000 mg/kg), or levofloxacin (1000 mg/kg) induced no convulsions in mice. In contrast, some nonsteroidal anti-inflammatory drugs (NSAIDs), fenbufen (200 mg/kg), indomethacin (500 mg/kg), and naproxen (500 mg/kg) induced convulsions in combination with the majority of the new quinolones tested. gamma-Aminobutyric acid (GABA)(A) receptor blockade-mediated neuronal excitation is assumed to be involved in these toxic convulsions. Enoxacin (100 microM) and lomefloxacin (100 microM) only slightly reduced [3H]muscimol binding to GABA(A) receptors in mouse whole brain membrane. However, these reductions were markedly enhanced by the addition of fenbufen (100 microM), indomethacin (100 microM), or naproxen (100 microM). Conversely, celecoxib (100 microM) had no apparent effect on [3H]muscimol binding when applied alone or in combination with enoxacin or lomefloxacin. These results suggest that celecoxib may be a more desirable anti-inflammatory agent with respect to drug interactions with new quinolones compared with some conventional NSAIDs.
Yoshino
Taiji
T
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan. yoshino@yamanouchi.co.jp
Noguchi
Masahiro
M
Okutsu
Hiroko
H
Kimoto
Aishi
A
Sasamata
Masao
M
Miyata
Keiji
K
D000818:Animals; D000068579:Celecoxib; D008297:Male; D051379:Mice; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011720:Pyrazoles / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D015363:Quinolones / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D013449:Sulfonamides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity
D011720:Pyrazoles; D015363:Quinolones; D011963:Receptors, GABA-A; D013449:Sulfonamides; D000068579:Celecoxib