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The kappa-opioid agonist (+/-)-bremazocine elicits peripheral antinociception by activation of the L-arginine/nitric oxide/cyclic GMP pathway.
Eur J Pharmacol. 2002 Nov 01; 454(1):19-23.EJ

Abstract

In view of the scarce information about the analgesic mechanism of kappa-opioid receptor agonists, the objective of the present study was to determine whether nitric oxide (NO) is involved in the peripheral antinociception of bremazocine, a kappa-opioid receptor agonist. Three drugs all interfering with the L-arginine/NO/cyclic GMP pathway were tested using the rat paw model of carrageenan-induced (250 microg) hyperalgesia: (a) N(G)-nitro-L-arginine (a nonselective NO-synthase inhibitor), (b) methylene blue (a guanylate cyclase inhibitor), and (c) zaprinast (a cyclic GMP phosphodiesterase inhibitor). Intraplantar administration of bremazocine (20, 40 and 50 microg) caused a dose-dependent peripheral antihyperalgesia against carrageenan-induced hyperalgesia. The possibility of the higher dose of bremazocine (50 microg) having central or systemic effect was excluded since administration of the drug into the left paw did not elicit antinociception in the contralateral paw. However, when the dose of bremazocine was increased to 100 microg, a significant increase in the nociceptive threshold was observed, as measured in the hyperalgesic contralateral paw. Peripheral antihyperalgesia induced by bremazocine (50 microg) was significantly reduced in a dose-dependent manner when N(G)-nitro-L-arginine (6, 9, 12 and 25 microg) or methylene blue (250, 375 and 500 microg) was injected before. Previous treatment with 50 microg of zaprinast (which had no effect when administered alone) potentiated the antihyperalgesic effect of bremazocine (20 microg). Our data suggest that bremazocine elicits peripheral antinociception by activation of the L-arginine/NO/cyclic GMP pathway and that nitric oxide is an intermediary in this mechanism, forming cyclic GMP.

Authors+Show Affiliations

Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Campus da Pampulha, Belo Horizonte, MG 31270-100, Brazil.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12409000

Citation

Amarante, Luiz H., and Igor Dimitri Gama Duarte. "The Kappa-opioid Agonist (+/-)-bremazocine Elicits Peripheral Antinociception By Activation of the L-arginine/nitric Oxide/cyclic GMP Pathway." European Journal of Pharmacology, vol. 454, no. 1, 2002, pp. 19-23.
Amarante LH, Duarte ID. The kappa-opioid agonist (+/-)-bremazocine elicits peripheral antinociception by activation of the L-arginine/nitric oxide/cyclic GMP pathway. Eur J Pharmacol. 2002;454(1):19-23.
Amarante, L. H., & Duarte, I. D. (2002). The kappa-opioid agonist (+/-)-bremazocine elicits peripheral antinociception by activation of the L-arginine/nitric oxide/cyclic GMP pathway. European Journal of Pharmacology, 454(1), 19-23.
Amarante LH, Duarte ID. The Kappa-opioid Agonist (+/-)-bremazocine Elicits Peripheral Antinociception By Activation of the L-arginine/nitric Oxide/cyclic GMP Pathway. Eur J Pharmacol. 2002 Nov 1;454(1):19-23. PubMed PMID: 12409000.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The kappa-opioid agonist (+/-)-bremazocine elicits peripheral antinociception by activation of the L-arginine/nitric oxide/cyclic GMP pathway. AU - Amarante,Luiz H, AU - Duarte,Igor Dimitri Gama, PY - 2002/11/1/pubmed PY - 2003/6/20/medline PY - 2002/11/1/entrez SP - 19 EP - 23 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 454 IS - 1 N2 - In view of the scarce information about the analgesic mechanism of kappa-opioid receptor agonists, the objective of the present study was to determine whether nitric oxide (NO) is involved in the peripheral antinociception of bremazocine, a kappa-opioid receptor agonist. Three drugs all interfering with the L-arginine/NO/cyclic GMP pathway were tested using the rat paw model of carrageenan-induced (250 microg) hyperalgesia: (a) N(G)-nitro-L-arginine (a nonselective NO-synthase inhibitor), (b) methylene blue (a guanylate cyclase inhibitor), and (c) zaprinast (a cyclic GMP phosphodiesterase inhibitor). Intraplantar administration of bremazocine (20, 40 and 50 microg) caused a dose-dependent peripheral antihyperalgesia against carrageenan-induced hyperalgesia. The possibility of the higher dose of bremazocine (50 microg) having central or systemic effect was excluded since administration of the drug into the left paw did not elicit antinociception in the contralateral paw. However, when the dose of bremazocine was increased to 100 microg, a significant increase in the nociceptive threshold was observed, as measured in the hyperalgesic contralateral paw. Peripheral antihyperalgesia induced by bremazocine (50 microg) was significantly reduced in a dose-dependent manner when N(G)-nitro-L-arginine (6, 9, 12 and 25 microg) or methylene blue (250, 375 and 500 microg) was injected before. Previous treatment with 50 microg of zaprinast (which had no effect when administered alone) potentiated the antihyperalgesic effect of bremazocine (20 microg). Our data suggest that bremazocine elicits peripheral antinociception by activation of the L-arginine/NO/cyclic GMP pathway and that nitric oxide is an intermediary in this mechanism, forming cyclic GMP. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/12409000/The_kappa_opioid_agonist__+/___bremazocine_elicits_peripheral_antinociception_by_activation_of_the_L_arginine/nitric_oxide/cyclic_GMP_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014299902022756 DB - PRIME DP - Unbound Medicine ER -