SUBGROUPS AMONG MU-OPIOID RECEPTOR AGONISTS DISTINGUISHED BY ATP-SENSITIVE K-ACTING DRUGS( CHANNEL)

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.