Role of L-arginine/nitric oxide pathway in the antinociceptive activities of morphine and mepyramine in mice.
The p-benzoquinone (PBQ)-induced abdominal constriction test was used to assess the involvement of L-arginine/nitric oxide (NO) pathway in the antinociceptive activity of the subcutaneously administered H1-receptor antagonist, mepyramine (CAS 59-33-6), and an opioid receptor agonist, morphine (CAS 57-27-2), in mice. Mepyramine (ED50: 5.6 mg/kg) and morphine (ED50: 0.13 mg/kg) produced antinociceptive effects. The NO precursor L-arginine (CAS 1119-34-2) (50 mg/kg) also produced antinociception similar to mepyramine, but significantly less than morphine. The NO synthase (NOS) inhibitor L-NG-monomethylarginine (L-NMMA) (CAS 53308-83-1) (50 mg/kg) did not significantly change p-benzoquinone-induced abdominal constrictions. L-arginine significantly increased the antinociceptive effects of morphine and mepyramine. The antinociceptive activity of morphine, but not that of mepyramine, was completely abolished when combined with L-NMMA. L-NMMA also significantly decreased the antinociception induced by morphine or mepyramine in combination with L-arginine. The present results suggest that morphine and mepyramine could produce peripheral antinociception by the involvement of L-arginine/NO cascade or other related pathways of nociceptive processes induced by NO.
Abacioğlu
N
N
Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey. nabaci@farma.net.tr
Ozmen
R
R
Cakici
I
I
Tunçtan
B
B
Kanzik
I
I
D000005:Abdomen; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000502:physiology*; D016227:Benzoquinones; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010147:Pain Measurement / Q000187:drug effects; D011738:Pyrilamine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000701:Analgesics, Opioid; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D009020:Morphine; D001120:Arginine; D019001:Nitric Oxide Synthase; D011738:Pyrilamine