Diltiazen enhances and flunarizine inhibits nimodipine's antiseizure effects

M. A. Morón, C. W. Stevens, T. L. Yaksh

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The dihydropyridine calcium channel antagonist, nimodipine has antiepileptic and anticonvulsive properties that are thought to be mediated through neuronal calcium channel blockade. The dihydropyridine binding site can be positively and negatively allosterically regulated by the benzothiazepines and the phenylalkylamines/piperazines, respectively. We investigated this binding interaction at the physiologic level by examining the effects of diltiazem (a benzothiazepine) and flunarizine (a piperazine) on the antiseizure activity of nimodipine. Seizures were induced with pentylenetetrazole in awake rats with chronically implanted EEG electrodes. Calcium channel antagonists were administered intracerebroventricularly 30 min after pentylenetytrazole at doses given at 15 min intervals. Diltiazem and flunarizine alone lacked antiseizure properties. The calculated ED50 values for nimodipine were: nimodipine alone = 135 μg; nimodipine + diltiazem (100 μg) = 67 μg. Nimodipine + flunarizine (10 μg) completely suppressed nimodipine's antiseizure activity. These findings may reflect the interaction observed among these agents at binding sites associated with the calcium channel and supports the idea that dihydropyridines mediate their antiseizure actions through neuronal calcium channel antagonism.

Original languageEnglish
Pages (from-to)299-307
Number of pages9
JournalEuropean Journal of Pharmacology
Volume163
Issue number2-3
DOIs
StatePublished - 25 Apr 1989

Fingerprint

Flunarizine
Nimodipine
Diltiazem
Calcium Channels
Calcium Channel Blockers
Piperazines
Binding Sites
Dihydropyridines
Implanted Electrodes
Pentylenetetrazole
Anticonvulsants
Electroencephalography
Seizures

Keywords

  • Ca channel antagonists
  • Dihydropyridines
  • Diltiazem
  • Flunarizine
  • Nimodipine
  • Seizures

Cite this

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abstract = "The dihydropyridine calcium channel antagonist, nimodipine has antiepileptic and anticonvulsive properties that are thought to be mediated through neuronal calcium channel blockade. The dihydropyridine binding site can be positively and negatively allosterically regulated by the benzothiazepines and the phenylalkylamines/piperazines, respectively. We investigated this binding interaction at the physiologic level by examining the effects of diltiazem (a benzothiazepine) and flunarizine (a piperazine) on the antiseizure activity of nimodipine. Seizures were induced with pentylenetetrazole in awake rats with chronically implanted EEG electrodes. Calcium channel antagonists were administered intracerebroventricularly 30 min after pentylenetytrazole at doses given at 15 min intervals. Diltiazem and flunarizine alone lacked antiseizure properties. The calculated ED50 values for nimodipine were: nimodipine alone = 135 μg; nimodipine + diltiazem (100 μg) = 67 μg. Nimodipine + flunarizine (10 μg) completely suppressed nimodipine's antiseizure activity. These findings may reflect the interaction observed among these agents at binding sites associated with the calcium channel and supports the idea that dihydropyridines mediate their antiseizure actions through neuronal calcium channel antagonism.",
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Diltiazen enhances and flunarizine inhibits nimodipine's antiseizure effects. / Morón, M. A.; Stevens, C. W.; Yaksh, T. L.

In: European Journal of Pharmacology, Vol. 163, No. 2-3, 25.04.1989, p. 299-307.

Research output: Contribution to journalArticle

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