Trileptal

Tadalafil (kindly provided by Polpharma S.A., Starogard Gdański, Poland), clonazepam (Clonazepamum, Polfa, Warsaw, Poland), oxcarbazepine (Trileptal, Novartis, Warsaw, Poland), tiagabine (Gabitril, Sanofi Winthrop, Gentilly, France), carbamazepine (kindly provided by Polpharma S.A., Starogard Gdański, Poland), and topiramate (Topamax, Janssen-Cilag International NV, Beerse, Belgium) were suspended in a 1% solution of Tween 80 (POCH, Gliwice, Poland). Valproate (as sodium salt, Sigma-Aldrich) was dissolved in normal saline. The pretreatment time for tadalafil (90 min) was based on pharmacokinetic study results (see Fig. 1). Tiagabine and Valproate were administered 15 min, clonazepam and oxcarbazepine 30 min, while carbamazepine and topiramate 60 min prior to the tests. All drug solutions/suspensions were prepared freshly and administered intraperitoneally (i.p.) at a volume of 0.1 ml per 10 g of body weight. Control animals received respective vehicles only.Fig. 1

Serum and brain concentrations of tadalafil in mice. Data are presented as the mean ± SEM. Tadalafil (20 mg/kg) was injected i.p. 30, 60, 90, 120, and 240 min before mice decapitation. Experimental groups consisted of 6–10 animals. Serum and brain concentrations of tadalafil are expressed in ng/ml and ng/g, respectively

Amiodarone (Opacorden, Polpharma, Starogard Gdański, Poland), lamotrigine (Lamitrin, GlaxoSmithKline, Brentford, Middlesex, UK), oxcarbazepine (Trileptal, Novartis, Nürnberg, Germany), topiramate (Topamax, Janssen-Cilag International NV, Beerse, Belgium), pregabalin (Lyrica, Pfizer Limited, Sandwich, Kent, UK) were suspended in a 1% aqueous solution of Tween 80 (Sigma-Aldrich, St. Louis, MO, USA). All drugs or vehicle (in control groups) were administered intraperitoneally (i.p.) in a volume of 10 mL/kg body weight. Amiodarone and oxcarbazepine were applied 30 min., lamotrigine and topiramate 60 min., pregabalin 120 min. before tests, respectively. Doses of antiepileptic drugs and amiodarone, as well as their application time, were based on our experimental experiences published elsewhere [2 (link),16 (link)].

In the study, the following drugs were used: antiarrhythmic drug—mexiletine (Sigma-Aldrich, Slovakia), antiepileptic drugs: lamotrigine (Lamitrin, GlaxoSmithKline, Great Britain), oxcarbazepine (Trileptal, Novartis Pharma, Germany), pregabalin (Lyrica, Pfizer, Great Britain), topiramate (Topamax, Janssen-Cilag, Belgium). mexiletine was dissolved in distilled water whereas antiepileptic drugs were suspended in 1% solution of Tween 80 (Sigma, St. Louis, MO, USA). Drug solutions were prepared freshly on each day of tests. All examined drugs were administered intraperitoneally in a volume of 10 ml/kg of body weight: mexiletine—15 min, oxcarbazepine—30 min, lamotrigine—60 min, topiramate—60 min, while pregabalin—120 min before the tests.