A protein kinase inhibitor, H-7, inhibits the development of tolerance to opioid antinociception.
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.
Narita
M
M
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
Feng
Y
Y
Makimura
M
M
Hoskins
B
B
Ho
I K
IK
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
D007546:Isoquinolines; D010879:Piperazines; D009020:Morphine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002077:Butorphanol