1 The effects of BRL 34915 (cromakalim), a potassium channel opener, have been tested on the epileptiform activity elicited by high doses/concentrations of some calcium antagonists in in vivo (diltiazem) and in vitro (diltiazem and verapamil) experiments in rats. 2 Diltiazem (150–300 mg kg−1, i.p.) induced behavioural and electroencephalographic (EEG) seizures that were completely prevented by cromakalim (10 nmol/10μl, i.c.v.). Whereas, pentobarbitone (5–10 mg kg−1, i.p.) only prevented the behavioural component of the seizures. 3 In hippocampal slices, verapamil (1.5–2.0 mm) produced, within 30–60 min of perfusion, a CAl epileptiform bursting in 80% of the experiments. This epileptiform activity was prevented by the cromakalim concentration (50 μm) that did not affect the control CAl synaptic transmission per se. Pentobarbitone also prevented verapamil‐induced epileptiform bursting only at the concentration (100 μm) that also reduced control CAl synaptic transmission. 4 Diltiazem (1.5 mm) produced a biphasic excitatory‐depressant effect within 60 min of perfusion. A CAl epileptiform bursting appeared in 100% of the experiments within 30 min of perfusion. These excitatory effects were followed by a depression phase, characterized by a reduction of the magnitude of CAl excitatory postsynaptic potentials (e.p.s.ps) and population spike. 5 The diltiazem‐induced epileptiform bursting was prevented by cromakalim at a concentration (50 μm) that did not affect the control CAl synaptic transmission per se. Pentobarbitone also prevented the diltiazem‐induced epileptiform bursting only at a concentration (100 μm) that also reduced the control CAl synaptic transmission. Both cromakalim (50 μm) and pentobarbitone (100 μm) failed to affect the depressant effects of diltiazem on CAl hippocampal area. On the contrary, high (3.3 mm) calcium solutions prevented both the excitatory and the depressant effects of 1.5 mm diltiazem within 60 min. 6 These data indicate an involvement of potassium currents in the epileptiform activity elicited by high doses of diltiazem and verapamil.
British Journal of Pharmacology – Wiley
Published: Dec 1, 1991
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