The Effects of Methylene Blue and Tadalafil in Pentylenetetrazole Induced Convulsion Model

Abstract

L-arginine (L-ARG)-nitric oxide (NO)–cGMP (cyclic guanosine monophosphate) cycle has been determined in various studies to be associated with epilepsy. Tadalafil is a potent inhibitor of phosphodiesterase 5 (PDE5) and increases the level of cGMP. Methylene blue (MB) is a lipophilic agent regulating intracellular electron flow as well as increasing the mitochondrial effectiveness. It also decreases cGMP levels by directly inhibiting guanylate cyclase.The aim of the present study was to evaluate the effects of MB and tadalafil on pentylenetetrazol-induced seizures. MB and tadalafil were administered 30 min prior to PTZ (70 mg/kg, i.p.) injection and the dose-response ratio was determined. Racine's Convulsion Scale and first myoclonic jerk (FMJ) onset time was used to evaluate seizures. Besides, drugs were administered 30 min prior to pentylenetetrazol (35 mg/kg, i.p.) injection and EEG was recorded from cortex and the spike wave discharges was determined in EEG. Plasma cGMP levels were measured in all groups. 5 and 10 mg/kg MB decreased Racine convulsion stage, increased FMJ onset time and decreased cGMP levels when compared with saline. 10 mg/kg tadalafil increased cGMP levels and Racine convulsion stage but decreased FMJ onset time compared with saline. Spike wave discharges were decreased in 5 and 10 mg/kg MB groups and increased in 10 mg/ kg tadalafil group when compared with saline group.The proconvulsant properties of all the agents may be taken into consideration, especially when prescribing PDE5 inhibitors.