Related Experiment Videos
Anticonvulsant effects of some calcium entry blockers in DBA/2 mice
G B De Sarro1, B S Meldrum, G Nisticó
1Institute of Pharmacology, Faculty of Medicine, University of Reggio Calabria, Italy.
Abstract:
1. The behavioural and anticonvulsant effects of several drugs acting by various mechanisms on calcium-channels or affecting intracellular Ca2+ concentrations were studied after both systemic and intracerebroventricular administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. 2. The anticonvulsant effects were evaluated on seizures evoked by means of auditory stimulation (109 dB) in animals placed singly under a perspex dome. 3. Flunarizine and dihydropyridine derivatives, belonging to class I of calcium entry blockers, administered intraperitoneally, were the most potent compounds. 4. Diltiazem, a benzothiazepine derivative belonging to class III, and HA 1004, a calcium antagonist, acting by inhibiting Ca2+ mobilization from intracellular stores, injected intraperitoneally, were 3-7.6 fold and 5.8-10.7 fold less potent than flunarizine respectively. 5. Verapamil and methoxyverapamil, two phenylalkylamine derivatives, given intraperitoneally, were completely ineffective in preventing sound-induced seizures in DBA/2 mice. In addition, high doses of verapamil and its methoxyderivative occasionally produced spontaneous tonic-clonic seizures. 6. After intracerebroventricular administration of the hydrosoluble calcium entry blockers, belonging to different classes, the anticonvulsant effects were similar to those observed after systemic administration. 7. The systemic administration of Bay K 8644, a dihydropyridine analogue, having the ability to stimulate calcium entry into cells produced a dose-dependent increase in clonic and tonic convulsions and other neurological side effects. 8. The present results strongly support the idea that some Ca2+ antagonists may be useful in human epilepsy.
Insights
Certain calcium channel blockers, like flunarizine, show potent anticonvulsant effects against sound-induced seizures in mice. These findings suggest potential therapeutic uses for calcium channel antagonists in treating human epilepsy.
Area of Science:
- Neuropharmacology
- Calcium Signaling
Background:
- Epilepsy is a neurological disorder characterized by recurrent seizures.
- Calcium ions play a critical role in neuronal excitability and seizure generation.
Purpose of the Study:
- To investigate the anticonvulsant effects of various calcium channel modulators.
- To assess the efficacy of these drugs in a genetic model of sound-induced seizures.
Main Methods:
- Systemic and intracerebroventricular administration of drugs in DBA/2 mice.
- Evaluation of anticonvulsant activity against seizures induced by auditory stimulation (109 dB).
Main Results:
- Flunarizine and dihydropyridine derivatives (Class I calcium entry blockers) demonstrated the highest potency.
- Diltiazem (Class III) and HA 1004 were less potent, while verapamil and methoxyverapamil were ineffective.
- Intracerebroventricular administration yielded similar anticonvulsant effects to systemic administration.
- Bay K 8644, a calcium entry enhancer, increased seizure severity and induced neurological side effects.
Conclusions:
- The study supports the potential utility of specific calcium channel antagonists in managing human epilepsy.
- Differential effects of various calcium channel blocker classes were observed in a sound-induced seizure model.