Subgroups among mu-opioid receptor agonists distinguished by ATP-sensitive K+ channel-acting drugs.
1. We evaluated the effects of the i.c.v. administration of different K+ channel blockers (gliquidone, 4-aminopyridine and tetraethylammonium) and an opener of K+ channels (cromakalim) on the antinociception induced by several mu-opioid receptor agonists in a tail flick test in mice. 2. The s.c. administration of all agonists of mu-opioid receptors tested (morphine, 1-16 mg kg-1; metadone, 1-6 mg kg-1; buprenorphine, 0.04-0.64 mg kg-1; fentanyl, 0.02-0.32 mg kg-1 and levorphanol, 0.2-3.2 mg kg-1) elicited a dose-dependent antinociceptive effect. 3. The ATP-sensitive K+ channel blocker, gliquidone (0.06-16 micrograms per mouse, i.c.v.) antagonized the antinociception induced by buprenorphine, morphine and metadone. In contrast, gliquidone (0.25-160 micrograms per mouse) did not modify the antinociceptive effects of fentanyl and levorphanol. 4. Cromakalim (4-64 micrograms per mouse, i.c.v.), an opener of ATP-sensitive K+ channels, enhanced the antinociception produced by buprenorphine, morphine, and methadone, and did not significantly modify the antinociceptive effects of fentanyl and levorphanol. 5. The i.c.v. administration of the K+ channel blockers tetraethylammonium (10 micrograms per mouse) or 4-aminopyridine (25 ng per mouse) did not significantly modify the antinociception induced by any mu-opioid receptor agonist tested. 6. These results suggest that the opening of ATP-sensitive K+ channels is involved in the antinociceptive effect of morphine, buprenorphine and methadone, but not in that of fentanyl or levorphanol. Consequently, we suggest that at least two subgroups can be distinguished among mu-opioid receptor agonists, each inducing antinociception through different effector mechanisms.
Ocaña
M
M
Department of Pharmacology and Neurosciences Institute, School of Medicine, University of Granada, Spain.
Del Pozo
E
E
Barrios
M
M
Baeyens
J M
JM
D015761:4-Aminopyridine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D005260:Female; D051379:Mice; D009474:Neurons / Q000187:drug effects; D010146:Pain / Q000503:physiopathology*; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D017450:Receptors, Opioid, mu; D013453:Sulfonylurea Compounds; D013757:Tetraethylammonium Compounds; D019806:Cromakalim; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine; C010969:gliquidone; D001418:Baclofen