Article date: 1991/3/1
PubMed ID: 2057453
Journal name: Pharmacology & toxicology (ISSN: 0901-9928)
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.
Author List: Ito T, Miura Y, Kadokawa T, Hori S, Shimada J, Miyahara T
Publication Types: Journal Article
Substances mentioned in the article: Anti-Inflammatory Agents, Non-Steroidal; Phenylacetates; Phenylbutyrates; Muscimol; Enoxacin; biphenylylacetic acid; Clorazepate Dipotassium; fenbufen; Baclofen; Pentobarbital; Bicuculline;
Mesh terms: Action Potentials/drug effects; Animals; Anti-Inflammatory Agents, Non-Steroidal/metabolism; Baclofen/pharmacology; Bicuculline/pharmacology; Clorazepate Dipotassium/pharmacology; Drug Interactions; Electric Stimulation; Enoxacin/pharmacology; Hippocampus/drug effects; In Vitro Techniques; Male; Muscimol/pharmacology; Pentobarbital/pharmacology; Phenylacetates/pharmacology; Phenylbutyrates/metabolism; Rats; Rats, Inbred Strains;