Riluzole prevents hyperexcitability produced by the mast cell degranulating peptide and dendrotoxin I in the rat.
Using electroencephalographic (EEG) recordings in freely moving rats and extracellular neuronal firing-rate recordings in hippocampal slices, we examined the effects of riluzole (RP 54274), a compound with anti-glutamate properties, against the convulsive seizures and the cellular hyperexcitability produced by the mast-cell degranulating peptide (MCD), dendrotoxin I (DTXi) and 4-aminopyridine (4-AP). I.c.v. administration of riluzole (10 nmol) prevented the seizures induced by MCD, and to a lesser extent those due to DIXi, whilst leaving 4-AP seizures unaffected. This effect was also present after oral administration of the compound (4 mg kg-1) and lasted for approximately 6 h. Electrophysiological recordings in vitro confirmed that riluzole dose dependently and reversibly abolished the sustained increase in firing rate induced by both MCD and DTXi in the hippocampus. These results indicate that the anti-epileptic spectrum of riluzole in this model has similarities with, but is not identical to, that of classical potassium channel openers, and differs from that of calcium channel blockers or other glutamate antagonists such as D(-)-2-amino-5-phosphono-valeric acid. However, since MCD releases glutamate, the preventive effect of riluzole in this model may involve direct or indirect interaction with glutamatergic processes.
Stutzmann
J M
JM
Rhône-Poulenc Santé, Centre de Recherches de Vitry, Unité d'électrophysiologie, Vitry Sur Seine, France.
Böhme
G A
GA
Gandolfo
G
G
Gottesmann
C
C
Lafforgue
J
J
Blanchard
J C
JC
Laduron
P M
PM
Lazdunski
M
M
D015761:4-Aminopyridine / Q000037:antagonists & inhibitors*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004569:Electroencephalography; D006624:Hippocampus; D007276:Injections, Intraventricular; D008297:Male; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D019782:Riluzole; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*
D000927:Anticonvulsants; D004546:Elapid Venoms; D010455:Peptides; D013844:Thiazoles; C008331:mast cell degranulating peptide; C020273:dendrotoxin; D019782:Riluzole; D015761:4-Aminopyridine