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

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-mu-g. 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-mu-g. After intravenous injection of LJC 10627, 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.