Anesthetic properties of riluzole (54274 RP), a new inhibitor of glutamate neurotransmission.
It has been suggested that some anesthetic agents could exert their hypnotic/anesthetic effects by selectively blocking receptors involved in the central excitatory neurotransmission mediated by glutamate. In the present study, we analyzed whether riluzole (54274 RP), a novel compound that inhibits both the release and some postsynaptic effects of glutamate in some brain structures, has anesthetic properties in rats. For this purpose, we investigated whether 1) riluzole administered intraperitoneally (ip) at doses ranging from 2.5 to 45 mg/kg induces loss of righting reflex (LRR); 2) riluzole (2.5 and 5 mg/kg) prolongs sleep-times induced by either ketamine (30 or 80 mg/kg ip) or thiopental (25 or 35 mg/kg ip); 3) a 5-mg/kg subanesthetic riluzole dose affects the minimum alveolar concentration of halothane (MACh). Onset of drug action was defined as the period of time from the ip injection to LRR. Sleep-time was considered the period of time from LRR to restoration of righting reflex. Riluzole at doses greater than 15 mg/kg was able to induce LRR (riluzole dose for which LRR was achieved in 50% of the rats [ED50 = 25.6 mg/kg]). A positive correlation was found between the dose of riluzole and sleep-time (r = 0.92, P less than 0.001). A 5-mg/kg (but not 2.5-mg/kg) riluzole dose significantly prolonged sleep-times induced by both ketamine (30 and 80 mg/kg) and thiopental (25 but not 35 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
Mantz
J
J
Department of Anesthesiology, Hopital Bichat, Paris, France.
Chéramy
A
A
Thierry
A M
AM
Glowinski
J
J
Desmonts
J M
JM
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D007274:Injections, Intraperitoneal; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012021:Reflex, Abnormal / Q000187:drug effects*; D019782:Riluzole; D012890:Sleep / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D013874:Thiopental / Q000494:pharmacology
D000777:Anesthetics; D018691:Excitatory Amino Acid Antagonists; D013844:Thiazoles; D018698:Glutamic Acid; D007649:Ketamine; D019782:Riluzole; D013874:Thiopental