NG-nitro-L-arginine prevents morphine tolerance.
NMDA receptor antagonists, such as MK-801, prevent the development of tolerance to morphine. Since many NMDA actions involve the production of nitric oxide, we examined the effects of a nitric oxide synthase inhibitor on morphine tolerance. The analgesic response to morphine (5 mg/kg s.c.) given daily diminishes from 60% in naive animals to 0% within 5 days. Coadministration of NG-nitro-L-arginine (8 mg/kg per day) along with morphine prevents the demonstration of appreciable tolerance for at least 11 days. These results suggest that morphine tolerance involves the activation of NMDA receptors followed by the subsequent release of nitric oxide.
Kolesnikov
Y A
YA
Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Pick
C G
CG
Pasternak
G W
GW
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D019335:Nitroarginine; D009569:Nitric Oxide; D009020:Morphine; D001120:Arginine