Daily mirfentanil induces (cross-) tolerance to the rate-decreasing effects of morphine and not mirfentanil.
The fentanyl derivative mirfentanil has a novel set of behavioral effects in non-humans including low-efficacy opioid actions and non-opioid antinociceptive actions. This study evaluated the rate-decreasing effects of mirfentanil, morphine, naltrexone and ketamine in pigeons both prior to and during a period of chronic treatment with mirfentanil (3.2-17.8 mg/kg/day). Daily treatment with mirfentanil did not modify the rate-decreasing effects of mirfentanil or ketamine; however, daily treatment decreased sensitivity to the rate-decreasing effects of morphine and increased sensitivity to naltrexone. These results demonstrate a lack of tolerance to an apparently non-opioid action (rate-decreasing effect) of mirfentanil, which might predict a lack of tolerance to the non-opioid antinociceptive actions of this compound. These results further indicate that cross-tolerance (to morphine) and dependence (increased sensitivity to naltrexone) can occur in the absence of tolerance (to mirfentanil).
Gauthier
C A
CA
Department of Pharmacology, Louisiana State University Medical Center, New Orleans 70112-1393, USA.
Bagley
J R
JR
Brockunier
L L
LL
France
C P
CP
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D010856:Columbidae; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology
D000700:Analgesics; D009271:Naltrexone; D007649:Ketamine; D009020:Morphine; C069209:mirfentanil; D005283:Fentanyl