Farelerde Pentilenetetrazol ile İndüklenen Epilepsi Modelinde Agmatinin Etkilerinin ve Nitrik Oksitin Katkısının Araştırılması

Abstract

Objective: Agmatine is an endogenous cationic amin and have been reported several neurotherapeutic effects through α2-adrenoceptors, imidazoline binding sites, inhibition of NMDA receptors and nitric oxide (NO) synthase. NO was reported to act as a neuromodulator and neurotransmitter in central nervous system and has proconvulsant/anticonvulsant activities in convulsion models. We aimed to compare the anticonvulsant activities of agmatine, sodium valproate, gabapentin and phenytoin, and to investigate the role of NO in effects of drugs. Material and Methods: Epilepsy seizures were induced in swiss-albino mice by single dose injection of penthylenetetrazole (PTZ) (60 mg/kg). Myoclonic-jerk (MJ) and generalized tonic-clonic seizures (GTCS) of mice were recorded. Agmatine (10 mg/kg), sodium valproate (150 mg/kg), gabapentin (20 mg/kg) and phenytoin (20 mg/kg) alone or in combinations with N(G)-Nitro-L-arginine-methyl-ester (L-NAME, 5 mg/kg), the precursor of NO, L-arginine (L-Arg, 60 mg/kg) and non-specific NO synthase inhibitor, were injected intraperitoneally. Results: While agmatine and sodium valproate significantly prevented GTCS%, phenytoin and gabapentin did not prevent. L-Arg significantly reduced activity of agmatine on MJ%. Both L-Arg and L-NAME did not affect activity of phenytoin on MJ% and GTCS%. L-Arg did not change the activity of gabapentin on MJ% and GTCS%. L-NAME significantly increased activity of gabapentin on MJ% and GTCS%. Conclusion: This study suggested that NO may have a role on anticonvulsant activity of agmatine and gabapentin but not those of sodium valproate and phenytoin.