Evidence for the role of nitric oxide in kappa-opiate tolerance in mice.
The hypothesis that inhibition of nitric oxide (NO) synthase with subsequent decrease in the production of NO might attenuate the development of kappa-opiate tolerance was examined. Concurrent treatment of NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA) (2-8 mg/kg, i.p.) along with U-50,488H (25 mg/kg, i.p.) twice daily for 4 days dose-dependently attenuated the development of tolerance to the analgesic and hypothermic effects of U-50,488H (25 mg/kg, i.p.). L-NMMA by itself did not modify the analgesic and hypothermic effects of acute administration of U-50,488H. A potential role for NO in the development of kappa-opiate tolerance is suggested.
Thorat
S N
SN
Department of Pharmacodynamics, University of Illinois at Chicago 60612.
Reddy
P L
PL
Bhargava
H N
HN
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase; D011759:Pyrrolidines / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D019323:omega-N-Methylarginine
D000700:Analgesics; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases