Anti-glutamatergic effect of riluzole: comparison with valproic acid.
Riluzole, an anti-amyotrophic lateral sclerosis drug, known to decrease presynaptic glutamate release, is viewed as a candidate supplementary medication for epilepsy. In the present study, we compared the effects of riluzole and valproate (VPA) in the pilocarpine-induced limbic seizure model and in the gamma-hydroxybutyrate lactone (GBL)-induced absence seizure model. We applied immunohistochemical study for vesicular transporter 1 (VGLUT1) and extracellular recording in the rat dentate gyrus of both pilocarpine- and GBL-induced seizure models to measure effects of riluzole and VPA. Both VPA and riluzole treatments reduced VGLUT1 immunoreactivity. Riluzole treatment completely inhibited pre-ictal spikes and spike-wave discharges in the pilocarpine- and GBL-induced epilepsy models, whereas VPA partially inhibited these phenomena. In both seizure models, the anti-epileptic effects of VPA and riluzole are basically related to anti-glutamatergic (reducing field excitatory postsynaptic potential slope and excitability ratio), not GABAergic (paired-pulse inhibition) effect. Riluzole was more effective at reducing seizure activity in both epilepsy models than VPA. These results suggest that riluzole is a potential antiepileptic drug with activity against limbic seizure and absence seizure.
Kim
J-E
JE
Department of Anatomy, College of Medicine, Hallym University, Chunchon 200-702, South Korea.
Kim
D-S
DS
Kwak
S-E
SE
Choi
H-C
HC
Song
H-K
HK
Choi
S-Y
SY
Kwon
O-S
OS
Kim
Y-I
YI
Kang
T-C
TC
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D012978:Sodium Oxybate; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*; D050598:Vesicular Glutamate Transport Protein 1 / Q000187:drug effects / Q000378:metabolism*
D000927:Anticonvulsants; D050598:Vesicular Glutamate Transport Protein 1; D010862:Pilocarpine; D014635:Valproic Acid; D012978:Sodium Oxybate; D019782:Riluzole