Effects of nifedipine on rhythmic synchronous activity of human neocortical slices

The antiepileptic effect of the dihydropyridine calcium channel blocker nif edipine was tested in neocortical slice preparations (n = 27) from patients ranging in age from four to 46 years (mean = 25) who underwent surgery for the treatment of intractable epilepsy. Epileptiform events consisted of sp ontaneously occurring rhythmic sharp waves as well as of untriggered epilep tiform field potentials induced by omission of Mg2+ from the superfusate, o r epileptiform field potentials elicited by application of bicuculline and triggered by single electrical stimuli. (1) Spontaneous rhythmic sharp wave s (n = 6): with nifedipine (40 mu mol/l), the repetition rate was decreased down to 30% of initial value, whereas the area under the field potential r emained nearly unchanged. (2) Untriggered low Mg2+ epileptiform field poten tials (n = 6): with nifedipine (40 mu mol/l) the area under the field poten tials was reduced while the action on the repetition rate was ambiguous. (3 ) Triggered bicuculline epileptiform field potentials (n = 15): with nifedi pine (40 mu mol/l; n = 4), no antiepileptic effect was found. There was, ho wever, a marked increase in the area under the epileptiform field potential s. The area under the field potentials was reduced only at a dosage of 60 m u mol/l (a = 11). This effect was stronger when nifedipine was applied with a K+ concentration raised from 4 to 8 mmol/l. The results show that the calcium channel blocker nifedipine is able to red uce differential epileptiform discharges in human neocortical tissue. These observations are in line with previous findings, suggesting that calcium A ux into neurons is involved in epileptogenesis. The present results therefo re support the idea that some organic calcium antagonists may be useful in human epilepsy therapy, although the etiology of epileptic seizures seems t o be a critical factor fur the efficacy of the drug. (C) 2000 IBRO. Publish ed by Elsevier Science Ltd. All rights reserved.