Abstract |
The dihydropyridine calcium antagonists nimodipine (NMD), PN200-110, and nicardipine were compared with phenytoin (PHT) as potential anticonvulsants in electrocortical shock (ECS)-induced seizures in the white New Zealand rabbit. Before treatment, seizure duration ranged from 43.8 +/- 5.1 to 49.6 +/- 5.2 s with an ECS stimulus of 10-V, 100-Hz, 0.1-ms pulses for 5 s. Each drug was administered into the right internal intracarotid artery 2 min before the ECS. A cumulative nimodipine dose of 440 micrograms/kg decreased seizure discharge to 6.6 +/- 5.0 s (p less than 0.001), whereas a total dose of 1.0 mg/kg PN200-110 was required to achieve a similar effect. Nicardipine was ineffective. A cumulative dose of 7 mg/kg phenytoin was required to suppress seizure discharge. These results indicate that Ca2+ channels modulated by dihydropyridines play a facilitating role in ECS-induced seizures. We propose that the anticonvulsant effects of nimodipine and PN200-110 are due to inhibition of neuronal calcium L-channels. Dihydropyridine Ca2+ antagonists that penetrate the blood-brain barrier (BBB) and bind to neuronal tissue may emerge as a novel class of anticonvulsants.
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Authors | F B Meyer, R E Anderson, T M Sundt Jr |
Journal | Epilepsia
(Epilepsia)
1990 Jan-Feb
Vol. 31
Issue 1
Pg. 68-74
ISSN: 0013-9580 [Print] United States |
PMID | 2137409
(Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Anticonvulsants
- Calcium Channel Blockers
- Dihydropyridines
- Oxadiazoles
- Nimodipine
- Phenytoin
- Nicardipine
- Isradipine
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Topics |
- Animals
- Anticonvulsants
(pharmacology)
- Calcium Channel Blockers
(pharmacology)
- Dihydropyridines
(pharmacology)
- Electroshock
- Isradipine
- Nicardipine
(pharmacology)
- Nimodipine
- Oxadiazoles
(pharmacology)
- Phenytoin
(pharmacology)
- Rabbits
- Seizures
(physiopathology)
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