Calcium modulation in epilepsy.
The ideal antiepileptic drug (AED) should correct the aberrant pathophysiology of epileptogenesis without interfering with normal neurotransmission A new group of drugs with antiepileptic efficacy, without sedative properties, would be an exciting prospect. Theoretical considerations and results from experimental animal models of epilepsy have put forward the possibility that calcium (Ca2+) antagonists may form such a group. The initiation of epileptogenic activity in the neuron is thought to be connected with the phenomenon known as "intrinsic burst firing", which is activated by an inward Ca2+ current. Ca2+ is described as the primary mediator of "excitotoxic" neuronal damage. Both necrotic and apoptotic cell death is associated with Ca2+ entry into the cells during status epilepticus. The Ca2+ channel blockers depressed epileptic depolarizations of neurons. In this review, we present anticonvulsant effects of cinnarizine, flunarizine, nifedipine, nimodipine, nicardipine, amlodipine, isradipine, niguldipine, diltiazem, verapamil and dantrolene in animal models of seizures. Also, a detailed analysis of interactions between Ca2+ blockers and AEDs was performed. Clinical trials in intractable epilepsy support to a certain degree antiepileptic properties of Ca2+ antagonists.
Kułak
Wojciech
W
Department of Pediatric Neurology and Rehabilitation, Medical University of Białystok, Waszyngtona 17, PL 15-274 Białystok, Poland.
Sobaniec
Wojciech
W
Wojtal
Katarzyna
K
Czuczwar
Stanisław J
SJ
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004827:Epilepsy / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology*; D006801:Humans; D011044:Poland
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D002118:Calcium