Epileptogenic activity induced by combined treatment with antiinflammatory drugs and enoxacin and its inhibition by a calcium antagonist, nicardipine.
Epileptogenic activity induced by combined treatment with antiinflammatory drugs and enoxacin was investigated in chronic electrode-implanted rats. Ferubinac ethyl and aspirin DL-lysine showed a spike and wave complex in EEG without showing remarkable behavioral changes when they were injected intraventricularly, although a relatively high dose was needed. Enoxacin, on the other hand, elicited potent epileptogenic activity characterized by uninterrupted high voltage spike and wave complex at doses of 50 and 100 micrograms. At the same time, rats showed hyperactivity, jumping and violent convulsion. Combined treatment with enoxacin (p.o.) and ferubinac ethyl (i.v.) caused potent epileptogenic activity characterized by uninterrupted burst of high voltage spike and wave complex. Behaviorally, animals showed forelimb clonus, head nodding and generalized convulsion. High voltage spike and wave complex was also observed after combined treatment with enoxacin (i. vent.) and ferubinac ethyl (i.v. or i. vent.) in association with hyperactivity and jumping and violent convulsion. Nicardipine remarkably inhibited epileptic seizures induced by combined treatment with enoxacin (p.o.) and ferubinac ethyl (i.v.). It is concluded that simultaneous treatment with enoxacin and ferubinac ethyl produced epileptogenic activity when injected intraventricularly, and nicardipine inhibited convulsions induced by combined use of enoxacin (p.o.) and ferubinac ethyl (i.v.).
Kamei
C
C
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Sugimoto
Y
Y
Ohishi
H
H
Okumura
Y
Y
Kitazumi
K
K
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D000893:Anti-Inflammatory Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D001241:Aspirin / Q000031:analogs & derivatives* / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004347:Drug Interactions; D004569:Electroencephalography / Q000187:drug effects; D015365:Enoxacin / Q000633:toxicity*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008239:Lysine / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced*
D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D015365:Enoxacin; D009529:Nicardipine; D008239:Lysine; D001241:Aspirin; C010395:acetylsalicylic acid lysinate