An in vivo evaluation of the antiseizure activity and acute neurotoxicity of agmatine.
Agmatine, an endogenous cationic amine, exerts a wide range of biological effects, including modulation of glutamate-activated N-methyl-D-aspartate (NMDA) receptor function in the central nervous system (CNS). Since glutamate and the NMDA receptor have been implicated in the initiation and spread of seizure activity, the capacity of agmatine to inhibit seizure spread was evaluated in vivo. Orally administered agmatine (30 mg/kg) protected against maximal electroshock seizure (MES)-induced seizure spread in rats as rapidly as 15 min and for as long as 6 h after administration. Inhibition of MES-induced seizure spread was also observed when agmatine was administered intraperitoneally. Agmatine's antiseizure activity did not appear to be dose-dependent. An in vivo neurotoxicity screen indicated that agmatine was devoid of any acute neurological toxicity at the doses tested. These preliminary data suggest that agmatine has promising anticonvulsant activity.
Bence
Aimee K
AK
Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0082, USA.
Worthen
David R
DR
Stables
James P
JP
Crooks
Peter A
PA
D000376:Agmatine / Q000008:administration & dosage* / Q000633:toxicity*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004827:Epilepsy / Q000188:drug therapy / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000927:Anticonvulsants; D000376:Agmatine