Effects of some quinolones on imipenem-induced seizures in DBA/2 mice.
1. The behavioural and convulsant effects of imipenem, a carbapenem derivative, were studied after i.p. administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures and in Swiss mice. 2. It was found that DBA/2 mice were more susceptible to seizures induced by imipenem than Swiss mice. 3. The proconvulsant effects of some quinolones were also evaluated in DBA/2 mice on seizures evoked by means of i.p. administration of imipenem. The present study demonstrated that the order of proconvulsant activity in our epileptic model was pefloxacin > enoxacin > ofloxacin > nalidixic acid > rufloxacin > norfloxacin > ciprofloxacin > cinoxacin > temafloxacin. 4. The relationship between the chemical structure and the proconvulsant activity of quinolone derivatives was studied. The relationship between the lipophilicity and the proconvulsant activity was also investigated. 5. Although the main mechanism for seizure potentiation cannot be easily determined potential drug interactions exist. It has been reported that imipenem and quinolones are all believed to increase excitation of the central nervous system by inhibition of GABA binding to receptors. 6. A slow clearance from the central nervous system and from the kidney may also occur following the concomitant administration of some quinolones and imipenem.
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
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De Sarro
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Ammendola
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De Sarro
D000161:Acoustic Stimulation; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000633:toxicity*; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects; D015378:Imipenem / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D007275:Injections, Intravenous; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008811:Mice, Inbred DBA; D008970:Molecular Weight; D009268:Nalidixic Acid / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology; D013045:Species Specificity; D013329:Structure-Activity Relationship
D000890:Anti-Infective Agents; D008055:Lipids; D009268:Nalidixic Acid; D015378:Imipenem