[Central stimulating effect of the combination of the new quinolone group of antimicrobials and nonsteroidal anti-inflammatory drugs in mice].
Six new quinolones: enoxacin, norfloxacin, ofloxacin, ciproflosacin, lomefloxacin, and tosufloxacin and eight nonsteroidal anti-inflammatory drugs: fenbufen, flurbiprofen, ketoprofen, pranoprofen, ibuprofen, indomethacin, mefenamic acid and aspirin were tested for their ability to produce a central stimulating effect in mice. At 5 min after the oral administration of one of the nonsteroidal anti-inflammatory drugs, a new quinolone was administered orally. The combination of drugs induced convulsions in a dose-dependent manner, and some mice died as a result of the convulsions. The survival time was used as an index to measure the intensity of convulsions induced by the drug combination. The new quinolones in combination with fenbufen at 100 mg/kg produced convulsions in the following order of potencies: enoxacin greater than lomefloxacin greater than norfloxacin. In contrast, administration of fenbufen together with ofloxacin, ciprofloxacin, or tosufloxacin up to a dose of 1000 mg/kg caused no convulsions. Four nonsteroidal anti-inflammatory drugs combined with enoxacin at 100 mg/kg also caused convulsion dose-dependently. The order of potency in producing convulsion was as follows: fenbufen greater than flurbiprofen greater than ketoprofen = pranoprofen. However, no convulsions were produced by treatment of ibuprofen, indomethacin, mefenamic acid or aspirin together with enoxacin. From these results, the important chemical structures of the new quinolones particularly concerned with the appearance of convulsion were discussed.
Murayama
S
S
Department of Pharmacology, School of Medicine, Chiba University, Japan.
Hara
Y
Y
Ally
A
A
Suzuki
T
T
Tamagawa
M
M
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects*; D012640:Seizures / Q000139:chemically induced*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015363:Quinolones