title: The 'glibenclamide-shift' of centrally-acting antinociceptive agents in mice.
abstract: Morphine-induced antinociception is antagonized by the K(+)-channel blocker glibenclamide (glyburide; Glib), implicating ATP-sensitive (KATP) K+ channels in the analgesic effect of opioids. The present study examined the generality of this conclusion by measuring the effect of Glib on supraspinal (intracerebroventricular; i.c.v.) antinociception produced by representative mu-opioids and the non-opioids pilocarpine and two alpha 2-adrenoceptor agonists (clonidine and tizanidine) using the mouse tail-flick test. Concurrent administration of Glib (40 micrograms, i.c.v.) produced a significant rightward shift of the dose-response curve of morphine, levorphanol, methadone, pilocarpine, clonidine and tizanidine; a modest, but not statistically significant, rightward shift of the dose-response curves of the mu-selective peptides DAMGO ([D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin) and PL017 ([N-Me-Phe3,D-Pro4]-morphiceptin); and no shift of the dose-response curves of alfentanil, carfentanil, fentanyl, sufentanil, or beta-endorphin. Glib produced a leftward shift of the dose-response curve of etorphine. These data support the involvement of KATP-type K+ channels in mediation of supraspinal antinociception, differentiate Glib-sensitive and Glib-insensitive opioid agonists, and reveal fundamental differences among antinociceptive agents in the extent of demonstrable utilization of this transduction pathway.
authors.affiliation: R.W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Raffa
authors.forename: R P
authors.initials: RP
authors.lastname: Martinez
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology*; D008297:Male; D008691:Methadone / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects
chemical_list: D000700:Analgesics; D015221:Potassium Channels; D009020:Morphine; D005905:Glyburide; D008691:Methadone