Tadalafil, a selective
phosphodiesterase type 5 inhibitor, is a long-acting oral agent for the treatment of
erectile dysfunction of multiple etiologies. Although
generalized tonic-clonic seizures were reported in a healthy man after taking
tadalafil, the influence of
tadalafil on seizure susceptibility has not been studied so far. Therefore, the aim of the present study was to investigate the effect of
tadalafil on seizure threshold as well as on the activity of some first- and second-generation
antiepileptic drugs in three acute seizure tests in mice. The obtained results showed that
tadalafil, at the highest dose tested (20 mg/kg), significantly decreased the threshold for the first myoclonic twitch in the intravenous
pentylenetetrazole (i.v. PTZ) seizure test. It did not affect the threshold for generalized clonic seizure and forelimb tonus in the i.v. PTZ, for tonic hindlimb extension in the maximal electroshock seizure threshold test, and for psychomotor seizure in the 6-Hz-induced seizure threshold test.
Tadalafil did not alter the
anticonvulsant activity of any of the studied
antiepileptic drugs in electrically induced seizure tests. Interestingly,
tadalafil potentiated the
anticonvulsant activity of
clonazepam and decreased the
anticonvulsant activity of
oxcarbazepine in the i.v. PTZ test. These interactions were pharmacodynamic in nature, as
tadalafil did not alter
clonazepam and
oxcarbazepine concentrations both in serum and brain tissue. Furthermore, neither
tadalafil alone nor its combinations with the studied
antiepileptic drugs produced any significant impairment of motor coordination (assessed in the chimney test), muscular strength (investigated in the grip-strength test), and long-term memory (assessed in the passive avoidance task). In conclusion,
tadalafil may increase the risk of myoclonic seizure and decrease the
anticonvulsant efficacy of
oxcarbazepine. Further studies are warranted to evaluate the safety of
tadalafil usage in patients with
epilepsy.