M. Ocana et Jm. Baeyens, DIFFERENTIAL-EFFECTS OF K-ADRENOCEPTOR, GABA(B) AND KAPPA-OPIOID RECEPTOR AGONISTS( CHANNEL BLOCKERS ON ANTINOCICEPTION INDUCED BY ALPHA(2)), British Journal of Pharmacology, 110(3), 1993, pp. 1049-1054
1 The effects of several K+ channel blockers (sulphonylureas, 4-aminop
yridine and tetraethylammonium) on the antinociception induced by clon
idine, baclofen and U50,488H were evaluated by use of a tail flick tes
t in mice. 2 Clonidine (0.125-2 mg kg-1, s.c.) induced a dose-dependen
t antinociceptive effect. The ATP-dependent K+ (K(ATP)) channel blocke
r gliquidone (4-8 mug/mouse, i.c.v.) produced a dose-dependent displac
ement to the right of the clonidine dose-response line, but neither 4-
aminopyridine (4-AP) (25-250 ng/mouse, i.c.v.) nor tetraethylammonium
(TEA) (10-20 mug/mouse, i.c.v.) significantly modified clonidine-induc
ed antinociception. 3 The order of potency of sulphonylureas in antago
nizing clonidine-induced antinociception was gliquidone>glipizide>glib
enclamide>tolbutamide, which is the same order of potency as these dru
gs block K(ATP) channels in neurones of the CNS. 4 Baclofen (2-16 mg k
g-1, s.c.) also induced a dose-dependent antinociceptive effect. Both
4-AP (2.5-25 ng/mouse, i.c.v.) and TEA (10-20 mug/mouse, i.c.v.) dose-
dependently antagonized baclofen antinociception, producing a displace
ment to the right of the baclofen dose-response line. However, gliquid
one (8-16 mug/mouse, i.c.v.) did not significantly modify the baclofen
effect. 5 None of the K+ channel blockers tested (gliquidone, 8-16 mu
g/mouse; 4-AP, 25-250 ng/mouse and TEA, 10-20 mug/mouse, i.c.v.), sign
ificantly modified the antinociception induced by U50,488H (8 mg kg-1,
s.c.). 6 These results suggest that the opening of K+ channels is inv
olved in the antinoceptive effect of alpha2 and GABA(B), but not kappa
-opioid, receptor agonists. The K+ channels opened by alpha2-adrenocep
tor agonists seem to be ATP-dependent channels, whereas those opened b
y GABA(B) receptor agonists are not.