Differential effects of dihydropyridine calcium channel blockers in kainic acid-induced experimental seizures in rats.
The anticonvulsant effects of the dihydropyridine calcium channel blockers nifedipine, nicardipine and nimodipine were studied on experimental seizures induced by intra-hippocampal injection of kainic acid (KA) in chloralhydrate anesthetized Wistar rats. The rats were anesthetized and placed in a stereotaxic apparatus. After midline incision four screw electrodes were placed over the left and right frontal and parietal cortex and KA was injected into left dorsal hippocampus via 5-microliter Hamilton microsyringe. The changes in electroencephalograph (EEG) activity and EEG power spectra were recorded in basal conditions and 5, 10, 15, 30 and 60 min following KA injection. KA-induced excitatory changes in the surface EEG activity were associated with the marked increase in EEG power spectra in the frequency range from 14.5-22 Hz. Pretreatment with nifedipine, nicardipine and nimodipine revealed that they exerted certain differences in their anticonvulsant properties. Nimodipine significantly delayed the onset of seizures and prevented the KA-induced changes in EEG and in EEG power spectra in all recorded channels and in a dose dependent manner. Nifedipine exerted significant anticonvulsant effect only in channel four, while nicardipine was ineffective. Our results suggest that anticonvulsant action of some dihydropyridine calcium channel blockers, especially nimodipine may be in part independent of its antagonism on L-type voltage-gated calcium (Ca(2+)) channels.
Kriz
Jasna
J
Department of Pharmacology, School of Medicine, University of Rijeka, Braće Branchetta 20/I, 51000, Rijeka, Croatia. mrav66@hotmail.com
Zupan
Gordana
G
Simonić
Ante
A
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004569:Electroencephalography; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid