Proconvulsant effects of sildenafil citrate on pilocarpine-induced seizures: involvement of cholinergic, nitrergic and pro-oxidant mechanisms.

Proconvulsant effects of sildenafil citrate on pilocarpine-induced seizures: involvement of cholinergic, nitrergic and pro-oxidant mechanisms.
Brain Res Bull. 2019 Apr 17;:
Authors: de Carvalho MAJ, Chaves Filho A, de Souza AG, de Carvalho Lima CN, de Lima KA, Rios Vasconcelos ER, Lima Feitosa M, Souza Oliveira JV, de Souza DAA, Macedo DS, de Souza FCF, de França Fonteles MM
Abstract
Sildenafil is a phosphodiesterase 5 inhibitor used for the treatment of erectile dysfunction and pulmonary hypertension. Proconvulsant effect is a serious adverse event associated with sildenafil use. Here, we investigated the possible proconvulsant effects of sildenafil in pilocarpine (PILO)-induced seizures model, which mimics some aspects of temporal lobe epilepsy. We also evaluated sildenafil's effects on hippocampal markers related to PILO-induced seizure, for instance, acetylcholinesterase (AChE) activity, oxidative stress and nitric oxide (NO) markers, namely nitrite, inducible NO synthase (iNOS) and neuronal NOS (nNOS). The influences of muscarinic receptors blockade on sildenafil proconvulsant effects and brain nitrite levels were also evaluated. Male mice were submitted to single or repeated (7 days) sildenafil administration (2.5, 5, 10 and 20 mg/kg). Thirty minutes later, PILO was injected and mice were further evaluated for 1 hour for seizure activity. Sildenafil induced a dose- and time-progressive proconvulsant effect in PILO-induced ...

Source: Brain Research Bulletin - April 16, 2019 Category: Neurology Authors: de Carvalho MAJ, Chaves Filho A, de Souza AG, de Carvalho Lima CN, de Lima KA, Rios Vasconcelos ER, Lima Feitosa M, Souza Oliveira JV, de Souza DAA, Macedo DS, de Souza FCF, de França Fonteles MM Tags: Brain Res Bull Source Type: research