Influence of opiate tolerance and calcium channel antagonists on the antinociceptive effects of L-arginine and NG-nitro L-arginine.
1. The antinociceptive effects induced by L-arginine (L-Arg 300-600 mg sc) or NG-nitro-L-arginine (NOArg 20-70 mg sc) in mice were assessed by the hot-plate test. 2. The antinociception induced by both agents was antagonized by naloxone. L-Arg significantly reduced the effects of the largest doses of morphine (3, 5, and 10 mg/kg) or pentazocine (7.5, 15, and 30 mg/kg). 3. Morphine antagonized L-Arg-induced antinociception but did not change the responses to NOArg. 4. Diltiazem (10 mg/kg) or verapamil (10 mg/kg) decreased L-Arg antinociceptive responses, whereas the effects of NOArg were enhanced. 5. The antinociceptive effects of L-Arg and NOArg were also tested in mice rendered tolerant to morphine or pentazocine. Whereas the effect of L-Arg were lower in tolerant animals, the responses to NOArg were unchanged. 6. The results suggest the involvement of opiate mechanisms and NO synthesis in L-ARG-induced antinociception and a lesser influence of opiate mechanisms in the antinociception induced by NOArg.
Contreras
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Departments of pharmacology, Faculty of Biological Sciences, Faculty of Pharmacy, University of Concepción, Chile.
Germany
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A
Gonzalez
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P
Norris
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B
D000698:Analgesia; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004361:Drug Tolerance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology*; D010147:Pain Measurement; D010423:Pentazocine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000701:Analgesics, Opioid; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009020:Morphine; D001120:Arginine; D014700:Verapamil; D019001:Nitric Oxide Synthase; D004110:Diltiazem; D010423:Pentazocine