Magnesium supplementation enhances the anticonvulsant potential of valproate in pentylenetetrazol-treated rats.
N-methyl-d-aspartate (NMDA) receptor antagonists appear to enhance the anticonvulsant activity of antiepileptic drugs in several models of epilepsy. Therefore, the current study evaluates the modulatory effect of magnesium (Mg(2+)), a non-competitive NMDA receptor antagonist, on a subprotective dose of valproate (VPA) against pentylenetetrazol (PTZ)-induced convulsions. Male Wister rats received either saline or PTZ (60mg/kg, i.p.). The other three groups were pretreated with Mg(2+) (40mg/kg, p.o., 4weeks), single subprotective dose of VPA (100mg/kg, i.p.), or Mg(2+) with VPA, before PTZ injection. PTZ provoked clonic convulsions, reduced GABA content, deranged brain redox status, and elevated nitric oxide (NO). Neither the subprotective dose of VPA nor Mg(2+) alone guarded against clonic seizures invoked by PTZ, an effect that was achieved only by their combination and supported by a significant delay in seizure latency. Moreover, VPA leveled off glycine and aspartate, exerted no effect on glutamate, and unexpectedly reduced GABA and taurine levels. Mg(2+) alone or in combination showed the same pattern on the aforementioned amino acids, except for taurine. All regimens restored glutathione (GSH) and total antioxidant capacity (TAC); however, only VPA normalized NO level. This study demonstrates that Mg(2+) could enhance the antiepileptic efficacy of a subprotective dose of VPA, possibly by improving redox balance and modulation of some brain amino acids.
Safar
Marwa M
MM
Departments of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Abdallah
Dalaal M
DM
Arafa
Nadia M
NM
Abdel-Aziz
Mohamed T
MT
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008274:Magnesium / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010433:Pentylenetetrazole; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D018709:Statistics, Nonparametric; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D005978:Glutathione; D008274:Magnesium; D010433:Pentylenetetrazole