7-Nitro indazole enhances methohexital anesthesia.
7-nitro indazole, a selective inhibitor of the neuronal nitric oxide (NO) synthase dose-dependently prolongs the duration of methohexital narcosis in the rat. This effect can be antagonized stereoselectively by the NO-synthase substrate l-arginine (l-Arg). The results support the assumption that the potentiation of the anesthetic state by NO-synthase inhibitors is due to a specific effect on brain NO-synthase and a disruption of synaptic NO signalling pathways. These results are also in accordance with predictions that follow from recent hypotheses proposing that a modification of the NMDA receptor function is the final common pathway of anesthetic action.
Motzko
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D
Brain Research Institute, University of Bremen, P.O.B. 330440, 28334 Bremen, Germany. motzko@zfn.uni-bremen.de
Glade
U
U
Tober
C
C
Flohr
H
H
D018686:Anesthetics, Intravenous; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D008723:Methohexital; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018686:Anesthetics, Intravenous; D004791:Enzyme Inhibitors; D007191:Indazoles; D008723:Methohexital; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole