Ars. Santos et al., The involvement of K+ channels and G(i/o) protein in the antinociceptive action of the gallic acid ethyl ester, EUR J PHARM, 379(1), 1999, pp. 7-17
The anti-hyperalgesic action, antinociception, and also the possible mechan
isms involved in the action of gallic acid ethyl ester (GAEE) isolated from
the aerial part of Phyllanthus urinaria, have been investigated in differe
nt models of chemical, mechanical and thermal nociception in mice and rats.
GAEE given by intraperitoneal (i.p.), oral (p.o.), intrathecal (i.t.) or b
y intracerebroventricular (i.c.v.) routes produced dose-related antinocicep
tion when assessed against chemical nociception in mice. GAEE significantly
inhibited the hyperalgesia induced by bradykinin or substance P in rat paw
, but did not affect the hyperalgesia caused by carrageenan or prostaglandi
n E-2. Furthermore, GAEE, in contrast to morphine, was completely ineffecti
ve in the hot-plate test in mice. The antinociception produced by GAEE (i.p
.) in the formalin test was significantly reversed by i.c.v. treatment of a
nimals with pertussis toxin and by i.t. administration of K+ channel blocke
rs such as apamin, charybdotoxin or glibenclamide, but not by tetraethylamm
onium. In contrast, GAEE (i.p.) antinociception was unaffected by i.p. trea
tment of animals with naloxone or by nitric oxide precursor, L-arginine, an
d this action was not secondary to its anti-inflammatory effect, nor was it
associated with non-specific effects such as muscle relaxation or sedation
. Thus, GAEE produces dose-dependent and pronounced systemic, spinal and su
praspinal antinociception in mice, probably via activation of K+ channels a
nd by a G(i/o) pertussis toxin-sensitive mechanism. (C) 1999 Elsevier Scien
ce B.V. All rights reserved.