Topiramate-antagonism of L-glutamate-induced paroxysms in planarians.
We recently reported that NMDA (N-methyl-D-aspartate) and AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) induce concentration-dependent paroxysms in planarians (Dugesia dorotocephala). Since the postulated mechanisms of action of the sulfamate-substituted monosaccharide antiepileptic drug topiramate include inhibition of glutamate-activated ion channels, we tested the hypothesis that topiramate would inhibit glutamate-induced paroxysms in our model. We demonstrate that: (1) L-glutamate (1-10 mM), but not D-glutamate, induced dose-related paroxysms, and that (2) topiramate dose-relatedly (0.3-3 mM) inhibited L-glutamate-induced paroxysms. These results provide further evidence of a topiramate-sensitive glutamate receptor-mediated activity in this model.
Raffa
Robert B
RB
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA 19140, USA. robert.raffa@temple.edu
Finno
Kristin E
KE
Tallarida
Christopher S
CS
Rawls
Scott M
SM
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D018698:Glutamic Acid / Q000008:administration & dosage / Q000633:toxicity*; D007536:Isomerism; D009043:Motor Activity / Q000187:drug effects; D010932:Planarians / Q000187:drug effects / Q000502:physiology; D000077236:Topiramate
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D000077236:Topiramate; D005632:Fructose; D018698:Glutamic Acid