title: A protein kinase inhibitor, H-7, inhibits the development of tolerance to opioid antinociception.
abstract: To investigate the effect of a protein kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), on the development of tolerance to antinociception induced by morphine (mu-opioid receptor agonist) and butorphanol (mu/delta/kappa-mixed opioid receptor agonist), rats were infused i.c.v. with morphine, butorphanol and H-7 through osmotic minipumps for 3 days. Concomitant infusion of H-7 dose dependently inhibited the development of tolerance to i.c.v. morphine- and butorphanol-induced antinociception. These results suggest that protein kinases may play an important role in the development of opioid tolerance.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
authors.forename: M
authors.initials: M
authors.lastname: Narita
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.forename: M
authors.initials: M
authors.lastname: Makimura
authors.forename: B
authors.initials: B
authors.lastname: Hoskins
authors.forename: I K
authors.initials: IK
authors.lastname: Ho
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002077:Butorphanol / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D004361:Drug Tolerance; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007546:Isoquinolines; D010879:Piperazines; D009020:Morphine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002077:Butorphanol