Pharmacological reports : PR · 2017
Sotalol enhances the anticonvulsant action of valproate and diphenylhydantoin in the mouse maximal electroshock model.
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Banach Monika, Popławska Monika, Borowicz-Reutt Kinga K
Аннотация
BACKGROUND: Sotalol as a drug blocking β-receptors and potassium KCNH2 channels may interact with different substances that affect seizures. Herein, we present interactions between sotalol and four conventional antiepileptic drugs: carbamazepine, valproate, phenytoin and phenobarbital.
METHODS: Effects of sotalol and antiepileptics alone on seizures were determined in the electroconvulsive threshold test, while interactions between sotalol and antiepileptic drugs were estimated in the maximal electroshock test in mice. Motor coordination and long-term memory were evaluated, respectively, in the chimney test and passive-avoidance task. Brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay.
RESULTS: Sotalol at doses up to 100mg/kg did not affect the electroconvulsive threshold. Applied at doses 60-100mg/kg, sotalol potentiated the antielectroshock action of valproate, while at doses 80-100mg/kg that of phenytoin. Sotalol (up to 100mg/kg) did not affect the action of carbamazepine or phenobarbital in the maximal electroshock. Sotalol alone and in combinations with antiepileptics impaired neither motor performance nor long-term memory in mice. Finally, sotalol did not change brain concentration of valproate and phenytoin, so pharmacokinetic interactions between the drugs are not probable.
CONCLUSIONS: As far as obtained data may be extrapolated into clinical conditions, sotalol may be considered as an arrhythmic drug that does not reduce the action of classical antiepileptic drugs and thereby can be used in epileptic patients with cardiac arrhythmias.
METHODS: Effects of sotalol and antiepileptics alone on seizures were determined in the electroconvulsive threshold test, while interactions between sotalol and antiepileptic drugs were estimated in the maximal electroshock test in mice. Motor coordination and long-term memory were evaluated, respectively, in the chimney test and passive-avoidance task. Brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay.
RESULTS: Sotalol at doses up to 100mg/kg did not affect the electroconvulsive threshold. Applied at doses 60-100mg/kg, sotalol potentiated the antielectroshock action of valproate, while at doses 80-100mg/kg that of phenytoin. Sotalol (up to 100mg/kg) did not affect the action of carbamazepine or phenobarbital in the maximal electroshock. Sotalol alone and in combinations with antiepileptics impaired neither motor performance nor long-term memory in mice. Finally, sotalol did not change brain concentration of valproate and phenytoin, so pharmacokinetic interactions between the drugs are not probable.
CONCLUSIONS: As far as obtained data may be extrapolated into clinical conditions, sotalol may be considered as an arrhythmic drug that does not reduce the action of classical antiepileptic drugs and thereby can be used in epileptic patients with cardiac arrhythmias.