Publication:


abstract

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.

Related Articles
Characterization of the anticonvulsant, behavioral and pharmacokinetic interaction profiles of stiripentol in combination with clonazepam, ethosuximide, phenobarbital, and valproate using isobolographic analysis.
Epilepsia. 2006
Characterization of the anticonvulsant, behavioral and pharmacokinetic interaction profiles of stiripentol in combination with clonazepam, ethosuximide, phenobarbital, and valproate using isobolographic analysis.
Luszczki JJ, Ratnaraj N, Patsalos PN, Czuczwar SJ. Epilepsia. 2006 Nov; 47(11):1841-54.
Effects of WIN 55,212-2 mesylate (a synthetic cannabinoid) on the protective action of clonazepam, ethosuximide, phenobarbital and valproate against pentylenetetrazole-induced clonic seizures in mice.
Prog Neuropsychopharmacol Biol...
Effects of WIN 55,212-2 mesylate (a synthetic cannabinoid) on the protective action of clonazepam, ethosuximide, phenobarbital and valproate against pentylenetetrazole-induced clonic seizures in mice.
Luszczki JJ, Andres-Mach M, Barcicka-Klosowska B, Florek-Luszczki M, Haratym-Maj A, Czuczwar SJ. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Dec 1; 35(8):1870-6. Epub 2011 Jul 18.
Acute exposure to caffeine decreases the anticonvulsant action of ethosuximide, but not that of clonazepam, phenobarbital and valproate against pentetrazole-induced seizures in mice.
Pharmacol Rep. 2006
Acute exposure to caffeine decreases the anticonvulsant action of ethosuximide, but not that of clonazepam, phenobarbital and valproate against pentetrazole-induced seizures in mice.
Luszczki JJ, Zuchora M, Sawicka KM, Kozińska J, Czuczwar SJ. Pharmacol Rep. 2006 Sep-Oct; 58(5):652-9.
Pharmacological and behavioral characteristics of interactions between vigabatrin and conventional antiepileptic drugs in pentylenetetrazole-induced seizures in mice: an isobolographic analysis.
Neuropsychopharmacology. 2005
Pharmacological and behavioral characteristics of interactions between vigabatrin and conventional antiepileptic drugs in pentylenetetrazole-induced seizures in mice: an isobolographic analysis.
Luszczki JJ, Wojcik-Cwikla J, Andres MM, Czuczwar SJ. Neuropsychopharmacology. 2005 May; 30(5):958-73.
Review A review of the preclinical pharmacology of tiagabine: a potent and selective anticonvulsant GABA uptake inhibitor.
Epilepsia. 1995
Review A review of the preclinical pharmacology of tiagabine: a potent and selective anticonvulsant GABA uptake inhibitor.
Suzdak PD, Jansen JA. Epilepsia. 1995 Jun; 36(6):612-26.