Evidence for a peripheral mechanism of action for the potentiation of the antinociceptive effect of morphine by dipyrone.

Abstract:

:The potentiation of the antinociceptive effect of morphine by dipyrone (metamizol) and the possible participation of a peripheral mechanism on such synergism were studied with the use of the formalin test in the rat. Nociception was induced by the intraplantar injection of diluted formalin (1%) in the right hind paw. Local administration of either dipyrone or morphine in the site of injury produced a dose-dependent antinociceptive effect. When combined, noneffective doses of morphine (1.25 microg/paw) and dipyrone (100 microg/paw) produced a significantly greater antinociceptive effect compared with either drug alone or saline. The opioid antagonist naloxone partly reversed the effect of the dipyrone-morphine combination. On the other hand, the inhibitor of nitric oxide (NO) synthesis, N(G)-L-nitro-arginine methylester (L-NAME), but not its inactive isomer, D-NAME, completely antagonized the effect of the dipyrone-morphine combination. These results suggest that the potentiation of morphine-induced antinociception by dipyrone in the formalin test requires an important participation of local release of NO, activating the NO-cyclic GMP pathway at the peripheral level.

authors

Aguirre-Bañuelos P,Granados-Soto V

doi

10.1016/s1056-8719(00)00046-0

keywords:

subject

Has Abstract

pub_date

1999-10-01 00:00:00

pages

79-85

issue

2

eissn

1056-8719

issn

1873-488X

pii

S1056-8719(00)00046-0

journal_volume

42

pub_type

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