Sildenafil citrate, a selective phosphodiesterase 5 (PDE5) inhibitor, is the first oral drug used in the therapy of erectile dysfunction. Presence of PDE5 in the brain and ability of sildenafil to cross the blood-brain barrier cause that this drug influences many central nervous systemrelated effects. Animal studies revealed that sildenafil has both proand anticonvulsant potential. It also influences activity of antiepileptic drugs in models of seizures in mice. The aim of the present study was to evaluate the effect of sildenafil on the psychomotor seizure threshold and activity of some classical antiepileptic drugs, i.e., valproic acid, phenobarbital, clonazepam and ethosuximide, in the 6 Hz seizure test in mice. We noted that sildenafil raises seizure threshold and enhances anticonvulsant action of the studied antiepileptic drugs in this test. Since sildenafil increases valproic acid concentration in mouse brain, interaction between these drugs had undesirable pharmacokinetic character. Sildenafil did not change concentration of the other studied antiepileptic drugs and thus noted interactions seem to be pharmacodynamic. Our results show that using sildenafil in epileptic patients should be safe and beneficial. Moreover, its combination with antiepileptic drugs might have both favourable and negative results and therefore it should be controlled in the clinical practice.
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