Effects of Sildenafil on Picrotxine‐Induced Seizures in Rat

Abstract

Sildenafil is a selective phosphodiesterase type 5 (PDE5) inhibitor which has been successfully used in the treatment of erectile dysfunction. However, several adverse effects are associated with its clinical use. Among numerous undesirable central nervous system effects, proconvulsant effects were reported in some patients using sildenafil. Sildenafil was also reported to have proconvulsant effects on pentylenetetrazole (PTZ)-induced clonic seizures in mice. By contrast, the drug exhibited weak anticonvulsant effects in amygdala-kindling seizures in rat. The aim of the present study is to examine the effects of sildenafil on picrtoxin (PTX)–induced clonic seizures using the timed intravenous infusion PTX threshold test in rat. The onset of generalized clonic seizures with loss of righting reflex was taken as the end point for determination of PTX seizure threshold. The experiments were conducted on male Sprague-Dawley rats weighing (280-300) gm. Different groups of rats were pretreated with various doses of sildenafil (5-20 mg/Kg).Control rats received an equal volume of saline. Sildenafil was administered intraperitoneally 30 min before intravenous infusion of PTX. Seizure threshold was calculated using the following formula: PTX (mg?Kg) = (Duration of infusion (s).infusion rate(ml/s).PTX concentration (mg/ml) )/(Body Wight (Kg)) The lowest dose of sildenafil (5g/Kg) did not significantly affect PTX clonic seizure threshold. However, higher doses (10,20 mg/Kg) significantly decrease PTX seizure threshold. Our data suggest that sildenafil has proconvulsant effects and are consistent with previous reports which demonstrated proconvulsant effects of sildenafil on the PTZ-induced clonic seizures in mice. Supported by a grant from Arabian Gulf University