Riluzole antagonizes the anxiogenic properties of the beta-carboline FG 7142 in rats.
The possible anxiolytic activity of riluzole, a drug which interferes with glutamic acid neurotransmission, was studied in rats using operant conflict procedures. In both "anxiolytic" and "anxiogenic" procedures, riluzole alone did not possess any anticonflict or proconflict effect at doses of 2 and 4 mg/kg PO. Riluzole over the same dose-range was able to antagonize the well known proconflict effect of the beta-carboline derivative FG 7142, an inverse agonist at the GABA-benzodiazepine-chloride ionophore receptor complex. This effect could be related to the possible interaction of riluzole with glutamic acid neurotransmission, since it has been demonstrated previously that beta-carbolines such as DMCM and beta-CCM were able to deplete the levels of aspartic and glutamic acids in rodent cortex, perhaps by enhancing release of amino acid neurotransmitters. If one subscribes to the hypothesis that the anxiety induced by beta-carboline derivatives is related to depression, riluzole might be of value in the treatment of anxiety related to depression.
Stutzmann
J M
JM
Rhône-Poulenc Santé, Centre de Recherches de Vitry, France.
Cintrat
P
P
Laduron
P M
PM
Blanchard
J C
JC
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001067:Appetite Depressants / Q000494:pharmacology*; D002243:Carbolines / Q000037:antagonists & inhibitors*; D003216:Conditioning, Operant / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D019782:Riluzole; D013844:Thiazoles / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D001067:Appetite Depressants; D002243:Carbolines; D013844:Thiazoles; C035874:FG 7142; D019782:Riluzole