Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Akademicka 19, Lublin, Poland.
J Neural Transm (Vienna). 2012 Aug;119(8):923-31. doi: 10.1007/s00702-012-0767-1.
The aim of the present study was to investigate the effect of sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, on threshold for clonic seizures in mice. In addition, the effects of sildenafil on the anticonvulsant activity of selected antiepileptic drugs (AEDs), i.e., clonazepam (CZP), valproate (VPA), phenobarbital (PB), ethosuximide (ETS) and tiagabine (TGB), were also evaluated. The subcutaneous pentylenetetrazole (PTZ) test was used to determine the effects of sildenafil on convulsive susceptibility and the anticonvulsant activity of the studied AEDs in mice, while the acute side effects of sildenafil and its combinations with the studied AEDs were evaluated in the chimney test, step-through passive-avoidance task and grip-strength test in mice. Total brain concentrations of AEDs were also determined. Sildenafil (5–40 mg/kg) did not influence the threshold for PTZ-induced clonic seizures in mice, but increased the anticonvulsant activity of ETS in this test without any significant changes in the total brain concentration. The activity of the remaining AEDs was not significantly changed by sildenafil. Neither sildenafil alone nor its combinations with the studied AEDs produced any changes in the motor coordination, long-term memory and muscular strength in mice. Co-administration of sildenafil with ETS in male epileptic patients with co-existing erectile dysfunctions might lead to the pharmacodynamic interactions that may be beneficial for the patients. Combinations of sildenafil with CZP, VPA, PB and TGB appear to be neutral in terms of their influence on seizures.
本研究旨在探讨选择性磷酸二酯酶 5（PDE5）抑制剂西地那非对小鼠阵挛性癫痫发作阈值的影响。此外，还评估了西地那非对所选抗癫痫药物（AEDs）的抗惊厥活性的影响，即氯硝西泮（CZP）、丙戊酸钠（VPA）、苯巴比妥（PB）、乙琥胺（ETS）和噻加宾（TGB）。戊四氮（PTZ）皮下测试用于确定西地那非对 convulsive 易感性和研究 AEDs 的抗惊厥活性的影响，而西地那非及其与研究 AEDs 的组合在烟囱测试、跨步式被动回避任务和握力测试中对急性副作用进行了评估在小鼠中。还确定了 AEDs 的总脑浓度。西地那非（5-40mg/kg）不影响小鼠 PTZ 诱导的阵挛性癫痫发作的阈值，但增加了 ETS 在该测试中的抗惊厥活性，而总脑浓度没有任何显著变化。其余 AEDs 的活性没有因西地那非而发生显著变化。西地那非单独或与研究 AEDs 的组合均未导致雄性癫痫患者的运动协调、长期记忆和肌肉力量发生变化。在合并存在勃起功能障碍的男性癫痫患者中西地那非与 ETS 联合使用可能会导致可能对患者有益的药效学相互作用。西地那非与 CZP、VPA、PB 和 TGB 的组合在其对癫痫发作的影响方面似乎是中性的。
