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Cromakalim (BRL 34915) counteracts the epileptiform activity elicited by diltiazem and verapamil in rats
Author(s) -
Popoli P.,
Pezzola A.,
Sagratella S.,
Zeng Y.C.,
Carolis A. Scotti
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12525.x
Subject(s) - diltiazem , bursting , verapamil , cromakalim , excitatory postsynaptic potential , chemistry , neurotransmission , population , anesthesia , medicine , pharmacology , endocrinology , calcium , agonist , neuroscience , biology , inhibitory postsynaptic potential , biochemistry , receptor , environmental health
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 m m ) 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 μ m ) that did not affect the control CAl synaptic transmission per se . Pentobarbitone also prevented verapamil‐induced epileptiform bursting only at the concentration (100 μ m ) that also reduced control CAl synaptic transmission. 4 Diltiazem (1.5 m m ) 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 μ m ) that did not affect the control CAl synaptic transmission per se . Pentobarbitone also prevented the diltiazem‐induced epileptiform bursting only at a concentration (100 μ m ) that also reduced the control CAl synaptic transmission. Both cromakalim (50 μ m ) and pentobarbitone (100 μ m ) failed to affect the depressant effects of diltiazem on CAl hippocampal area. On the contrary, high (3.3 m m ) calcium solutions prevented both the excitatory and the depressant effects of 1.5 m m 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.