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The epileptogenic effects of (1R, 5S, 6S)-2-[(6,7-dihydro-5H-pyrazolo[1,2-a][1,2,4]triazolium-6- yl)]thio-6-[(R)-1-hydroxyethyl]-1-methyl-carbapenem-3-carboxylate (LJC10627), a new derivative of carbapenem were studied in comparison with those of imipenem (imipenem/cilastatin), cefazolin and penicillin G. In intraventricular injection in rats, LJC10627 caused no epileptogenic activity at a dose of 32 micrograms. In contrast, imipenem, cefazolin and penicillin G showed dose-related seizure signs, continuous rhythmic spikes or high voltage spike-wave complexes and convulsive behaviors at doses higher than 10 micrograms. After intravenous injection of LJC10627, no epileptogenic signs on the electroencephalogram (EEGs) or in behavioral symptoms were observed, even at a dose of 500 mg/kg in rats and 300 mg/kg in rabbits, respectively. By contrast, imipenem/cilastatin provoked severe seizure patterns characterized by high voltage spikes-wave complex and convulsive behavior, both in rats and rabbits, using the same doses of LJC10627. Cefazolin and penicillin G also induced obvious epileptogenic signs in both rats and rabbits after intravenous injection. From these results, it was concluded that LJC10627, unlike imipenem (imipenem/cilastatin) and cefazolin, dose not elicit epileptogenic activity, and may therefore be safely used for clinical purpose.

journal of pharmacobio-dynamics

Comparative Study of Certain Antibiotics on Epileptogenic Property, Including (1Rpi, 5S, 6S)-2-((6,7-Dihydro-5H-pyrazolo(1,2-a)(1,2,4)triazolium-6-yl)thio-6-((R)-1-hydroxyethyl)-1-methyl-carbapenem-3-carboxylate (LJC10627), a Carbapenem Antibiotic with Broad Antimicrobial Spectrum.