Effect of Tadalafil on Seizure Threshold and Activity of Antiepileptic Drugs in Three Acute Seizure Tests in Mice

Abstract

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.

Modified behavioural tests to detect white matter injury- induced motor deficits after intracerebral haemorrhage in mice

“…The procedure was repeated three times, and the mean force exerted by each mouse before losing its grip was recorded. The mean force was then normalized to body weight and is expressed in mN/g 25–27 .…”

Effects of onopordia, a novel isolated compound from Onopordon acanthium, on pentylenetetrazole-induced seizures in mice: Possible involvement of nitric oxide pathway

“…An infusion pump (Harvard, USA) was employed in order to infuse PTZ at the constant rate of 1 ml/min. 20 Infusion was paused after observation of forelimb clonus followed by full clonus of the body. The dose of PTZ (mg/kg of mice weight) needed to induce clonic seizure was applied as an index of seizure threshold.…”

Erectile dysfunction in common neurological conditions: A narrative review

“…A study was to investigate the effect of tadalafil on seizure threshold in three acute seizure tests in mice. It concludes that tadalafil may increase the risk of myoclonic seizure and decrease the anticonvulsant efficacy of oxcarbazepine (129). In summary, PDE5i should be used with great caution in men with epilepsy.…”

“…In patients non-responsive to medical therapy disc surgery is indicated. Lumbosacral disc disease may interfere with the nerve transmission for erection through multiple autonomic and somatic pathways (129). (140).…”