Actions of BRL 34915 (Cromakalim) upon convulsive discharges in guinea pig hippocampal slices.

The effects of the purported K+ channel opener BRL 34915 upon CNS neurons were examined in guinea pig hippocampal slices. Both the EPSP component and the population spike of field potentials recorded in the CA1 area were reduced in amplitude by BRL 34915 (EC50 about 100 mumol/l). In the same concentration range, BRL 34915 also slowed down the bursting rate of pacemaker neurons in the CA3 region. In order to test a possible anticonvulsant efficacy of the drug, the excitability of hippocampal neurons was increased experimentally by changing the ionic composition of the perfusion medium (omission of Ca2+ or Mg2+, elevation of K+). In all three conditions, epileptiform neuronal activity occurred, which was depressed by BRL 34915. The similarity of the effects of BRL 34915 in normal and convulsive slices indicates that the compound acts upon intrinsic nonsynaptic processes controlling neuronal excitability and cell firing.