M. Ocana et al., SUBGROUPS AMONG MU-OPIOID RECEPTOR AGONISTS DISTINGUISHED BY ATP-SENSITIVE K-ACTING DRUGS( CHANNEL), British Journal of Pharmacology, 114(6), 1995, pp. 1296-1302
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 ind
uced by several mu-opioid receptor agonists in a tail flick test in mi
ce. 2 The s.c. administration of all agonists of mu-opioid receptors t
ested (morphine, 1-16 mg kg(-1); methadone, 1-6 mg kg(-1); buprenorphi
ne, 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 mu g per
mouse, i.c.v.) antagonized the antinociception induced by buprenorphin
e, morphine and methadone. In contrast, gliquidone (0.25-160 mu g per
mouse) did not modify the antinociceptive effects of fentanyl and levo
rphanol. 4 Cromakalim (4-64 mu g per mouse, i.c.v.), an opener of ATP-
sensitive K+ channels, enhanced the antinociception produced by bupren
orphine, morphine, and methadone, and did not significantly modify the
antinociceptive effects of fentanyl and levorphanol. 5 The i.c.v. adm
inistration of the K+ channel blockers tetraethylammonium (10 mu g per
mouse) or 4-aminopyridine (25 ng per mouse) did not significantly mod
ify the antinociception induced by any mu-opioid receptor agonist test
ed. 6 These results suggest that the opening of ATP-sensitive K+ chann
els is involved in the antinociceptive effect of morphine, buprenorphi
ne and methadone, but not in that of fentanyl or levorphanol. Conseque
ntly, we suggest that at least two subgroups can be distinguished amon
g mu-opioid receptor agonists, each inducing antinociception through d
ifferent effector mechanisms.