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Effects of some quinolones on imipenem-induced seizures in DBA/2 mice
A De Sarro1, D Ammendola, G De Sarro
1Institute of Pharmacology, School of Medicine, University of Messina, Italy.
Abstract:
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.
Insights
Imipenem and quinolone antibiotics can cause seizures, especially in susceptible mice. Pefloxacin showed the strongest proconvulsant effect, suggesting potential drug interactions and CNS excitation mechanisms.
Area of Science:
- Neuropharmacology
- Microbiology
- Drug Discovery
Background:
- Imipenem, a carbapenem antibiotic, exhibits behavioral and convulsant effects.
- Quinolone antibiotics are known to have potential neurotoxic side effects.
Purpose of the Study:
- To investigate the proconvulsant activity of imipenem and various quinolone derivatives.
- To evaluate the relationship between chemical structure, lipophilicity, and proconvulsant activity.
- To explore potential drug interactions between imipenem and quinolones.
Main Methods:
- Administration of imipenem and quinolones to DBA/2 mice (genetically epilepsy-prone) and Swiss mice.
- Evaluation of seizure susceptibility and proconvulsant effects.
- Analysis of structure-activity relationships and lipophilicity.
Main Results:
- DBA/2 mice were more susceptible to imipenem-induced seizures than Swiss mice.
- Pefloxacin demonstrated the highest proconvulsant activity among tested quinolones, followed by enoxacin, ofloxacin, and others.
- A correlation between chemical structure/lipophilicity and proconvulsant activity was observed.
Conclusions:
- Imipenem and quinolones may potentiate seizures through central nervous system excitation, potentially by inhibiting GABA binding.
- Potential for significant drug interactions exists with concomitant use.
- Slowed clearance of these drugs from the CNS and kidneys could contribute to adverse effects.