Effects of enoxacin and its combination with 4-biphenylacetate, an active metabolite of fenbufen, on population spikes in rat hippocampal slices.
The effects of enoxacin, a new quinolone antibacterial agent, and its combination with 4-biphenylacetate (BPA), an active metabolite of the non-steroidal antiinflammatory agent fenbufen, were examined on population spikes induced by electrical stimulation of the stratum radiatum in the CA1 pyramidal cell layer in rat hippocampal slices. Enoxacin (10(-4) M) and bicuculline (10(-6) M) increased the amplitude of the population spikes and anew elicited the second spikes (latency: 10 msec.), while BPA (10(-5) M) decreased the amplitude of the population spikes. However, the combination of enoxacin (10(-6), 10(-5) M) with BPA (10(-5) M) elicited the second spikes or epileptiform bursts with an increase of the population spike amplitude. The dose-response relationships showed that the effect of enoxacin was 100 times potentiated in the presence of BPA (10(-5) M). The second spikes induced by enoxacin (10(-4) M) were suppressed by muscimol (10(-6) M) and baclofen (10(-6) M), but not by clorazepate (5 x 10(-5) M) and pentobarbital (5 x 10(-5) M). The second spikes induced by bicuculline (10(-6) M) were suppressed by these four drugs. The second spikes by the combination of enoxacin (10(-6) M) with BPA (10(-5) M) were suppressed by muscimol (5 x 10(-6) M), but not by clorazepate (5 x 10(-5) M). These results suggest that the combination of enoxacin with BPA exerts a drug interaction to elicit the second spikes or epileptiform bursts with its mode of action different from that of bicuculline.
Ito
T
T
Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Suita/Osaka, Japan.
Miura
Y
Y
Kadokawa
T
T
Hori
S
S
Shimada
J
J
Miyahara
T
T
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D003009:Clorazepate Dipotassium / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D015365:Enoxacin / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010648:Phenylacetates / Q000494:pharmacology*; D010654:Phenylbutyrates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010648:Phenylacetates; D010654:Phenylbutyrates; D009118:Muscimol; D015365:Enoxacin; C012776:biphenylylacetic acid; D003009:Clorazepate Dipotassium; C010725:fenbufen; D001418:Baclofen; D010424:Pentobarbital; D001640:Bicuculline