Cromakalim (BRL 34915) counteracts the epileptiform activity elicited by diltiazem and verapamil in rats

Cromakalim (BRL 34915) counteracts the epileptiform activity elicited by diltiazem and verapamil... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Cromakalim (BRL 34915) counteracts the epileptiform activity elicited by diltiazem and verapamil in rats

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Publisher
Wiley
Copyright
1991 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
D.O.I.
10.1111/j.1476-5381.1991.tb12525.x
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

British Journal of PharmacologyWiley

Published: Dec 1, 1991

References

  • Anticonvulsant effects of some calcium entry blockers in DBA/2 mice
    SARRO, SARRO; MELDRUM, MELDRUM; NISTICO, NISTICO
  • A calcium‐activated hyperpolarization follows repetitive firing in hippocampal neurons
    HOTSON, HOTSON; PRINCE, PRINCE
  • Multiple effects of calcium antagonists on plateau currents in cardiac Purkinje fibers
    KASS, KASS; TSIEN, TSIEN
  • Divalent ions and the surface potential of charged phospholipid membranes
    MCLAUGHLIN, MCLAUGHLIN; SZABO, SZABO; EISENMAN, EISENMAN

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