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Differential effects of K + channel blockers on antinociception induced by α 2 ‐adrenoceptor, GABA B and κ‐opioid receptor agonists
Author(s) -
Ocaña Maria,
Baeyens José M.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13919.x
Subject(s) - glibenclamide , clonidine , chemistry , pharmacology , baclofen , tetraethylammonium , potency , channel blocker , opioid , agonist , endocrinology , receptor , medicine , in vitro , biochemistry , potassium , organic chemistry , calcium , diabetes mellitus
1 The effects of several K + channel blockers (sulphonylureas, 4‐aminopyridine and tetraethylammonium) on the antinociception induced by clonidine, baclofen and U50,488H were evaluated by use of a tail flick test in mice. 2 Clonidine (0.125–2 mg kg −1 , s.c.) induced a dose‐dependent antinociceptive effect. The ATP‐dependent K + (K ATP ) channel blocker gliquidone (4–8 μg/mouse, i.c.v.) produced a dose‐dependent displacement 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 μg/mouse, i.c.v.) significantly modified clonidine‐induced antinociception. 3 The order of potency of sulphonylureas in antagonizing clonidine‐induced antinociception was gliquidone > glipizide > glibenclamide > tolbutamide, which is the same order of potency as these drugs block K ATP channels in neurones of the CNS. 4 Baclofen (2–16 mg kg −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 μg/mouse, i.c.v.) dose‐dependently antagonized baclofen antinociception, producing a displacement to the right of the baclofen dose‐response line. However, gliquidone (8–16 μg/mouse, i.c.v.) did not significantly modify the baclofen effect. 5 None of the K + channel blockers tested (gliquidone, 8–16 μg/mouse; 4‐AP, 25–250 ng/mouse and TEA, 10–20 μg/mouse, i.c.v.), significantly modified the antinociception induced by U50,488H (8 mg kg −1 , s.c). 6 These results suggest that the opening of K + channels is involved in the antinoceptive effect of α 2 and GABA B , but not κ‐opioid, receptor agonists. The K + channels opened by α 2 ‐adrenoceptor agonists seem to be ATP‐dependent channels, whereas those opened by GABA B receptor agonists are not.