Differential antiepileptic effects of the organic calcium antagonists verapamil and flunarizine in neurons of organotypic neocortical explants from newborn rats

Abstract

Effects of the organic calcium antagonists verapamil and flunarizine on pentylenetetrazol induced paroxysmal depolarizations were tested in organotypic neocortical explants taken from neonatal rats. In these in vitro experiments the papaverin derivative verapamil depressed, and finally abolished, epileptic discharges in all cases. The piperazine derivative flunarizine, however, which is known to suppress epileptic discharges in hippocampal CA3 neurons (Bingmann and Speckmann 1986), showed no significant antiepileptic effects in the explanted neocortical neurons. Thus, the present findings may indicate that the suppressive action of flunarizine on the generation of paroxysmal depolarizations is restricted to distinct populations of neurons.

Upregulation of L-Type Ca2+Channels in Reactive Astrocytes after Brain Injury, Hypomyelination, and Ischemia

“…Work in hippocampal slice preparations has demonstrated that the lowering of the extracellular Ca 2ϩ concentration results in seizure-like tonic depolarization and rapid discharge of neurons (Yaari et al, 1986). Subsequently, epileptic depolarizations of single neurons and populations of neurons have been shown to be depressed by organic Ca 2ϩ channel blockers (Bingmann et al, 1988;Bingmann and Speckmann, 1989;Aicardi and Schwartzkroin, 1990;Pohl et al, 1992). The decrease in the extracellular concentration of Ca 2ϩ that occurs during seizures (Heinemann et al, 1977) has long been presumed to reflect an influx of Ca 2ϩ into discharging neurons via voltage-gated Ca 2ϩ channels.…”

Burst generation in neocortical neurons after GABA withdrawal in the rat

“…Mxed contribution of synaptic and voltage-dependent processes to G WS Voltage-dependent Ca2+ current in IB cells appears to be a major electrophysiological correlate of GWS at the neuronal level. However, in vivo administration of flunarizine has virtually no effect on GWS, although it is relatively active on verapamil-sensitive Ca2+ currents of neocortical neurons recorded in vitro (Bingmann et al 1988). In fact, epileptic activities during GWS involve both synaptic and intrinsic components.…”

Contribution of Calcium Ions to the Generation of Epileptic Activity and Antiepileptic Calcium Antagonism

“…In hippocampal slices of guinea pigs, PDSs elicit ed by pentylenetetrazole and caffeine are abolished by the organic calcium antagonists verapamil and flunarizine ( fig. 2A) [19][20][21], Verapamil and flunarizine are also able to depress PDSs evoked by the GABAa antagonists bicu culline and picrotoxin in neocortical and hippocampal slices ( fig. 2B) [22][23][24][25].…”

“…3) [26][27][28], Spontaneously occurring epileptic activity in neocortical and hippocam pal slices is also suppressed by verapamil [28]. A differ ential antiepileptic effect is apparent in organotypic tissue cultures of newborn rats: verapamil but not flunarizine depresses PDSs induced by pentylenetetrazole [20], The differential antiepileptic effect is not seen when epileptic activity is evoked by bicuculline in this preparation [24], PDSs induced in identified neurons of II. pomatia are suppressed by verapamil as well [29].…”