dizocilpine-maleate and fenbufen

The effects of drugs on the convulsions induced by the combination of a new quinolone antimicrobial, enoxacin, and a nonsteroidal anti-inflammatory drug, fenbufen, were studied in mice. The combination of enoxacin at 30 or 100 mg/kg, p.o. and fenbufen at 100 mg/kg, p.o. induced convulsions; and the mice died as a result of the convulsions. Pretreatment with either phenobarbital, phenytoin, valproic acid intraperitoneally, or morphine intravenously did not influence the convulsions. A high dose of diazepam or clonazepam prolonged the survival time, but could not prevent the mice from dying. After the occurrence of convulsions induced by enoxacin with fenbufen, administration of the excitatory amino acid antagonist MK-801 at 1 mg/kg, i.v. extended the survival time, even though all the mice died as a result of the convulsions. Simultaneous intravenous injections of MK-801 and diazepam suppressed the convulsions. This suppression was stronger than that produced by MK-801 or diazepam, injected separately. However, no mouse survived at the end. From these results, participation of both GABA-ergic and excitatory amino acidergic systems in the convulsions induced by enoxacin and fenbufen was discussed.

Topics: Amino Acids; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Diazepam; Dizocilpine Maleate; Drug Interactions; Drug Therapy, Combination; Enoxacin; gamma-Aminobutyric Acid; Male; Mice; Phenylbutyrates; Seizures

Interaction of quinolone antimicrobials and fenbufen, anti-inflammatory agents, with the N-methyl-D-aspartate (NMDA) receptor was investigated in rat hippocampal neurons with the conventional patch-clamp technique. Simultaneous applications of quinolones and a metabolite of fenbufen had no effects on the glutamate- and NMDA-induced currents. The blocking effects of Mg2+ and MK-801 on NMDA responses were also unaffected. Therefore, the convulsive action induced by quinolones and fenbufen does not seem to involve the function change of NMDA receptor.

Topics: 4-Quinolones; Animals; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Dizocilpine Maleate; Drug Interactions; Hippocampus; In Vitro Techniques; Magnesium; Neurons; Phenylbutyrates; Rats; Rats, Inbred Strains; Receptors, N-Methyl-D-Aspartate