Effects of nalfurafine on the reinforcing, thermal antinociceptive, and respiratory-depressant effects of oxycodone: modeling an abuse-deterrent opioid analgesic in rats.
Psychopharmacology (Berl)
; 234(17): 2597-2605, 2017 Sep.
Article
in En
| MEDLINE
| ID: mdl-28567699
ABSTRACT
RATIONALE Strategies to reduce the misuse of mu opioid agonists are critically needed. Previous work has shown that kappa opioid agonists can diminish the abuse-related effects and augment the antinociceptive effects of mu agonists. However, use of traditional kappa agonists is limited by their dysphoric side effects. OBJECTIVES:
The current study examined the effects of nalfurafine, a clinically available atypical kappa agonist, on the reinforcing, thermal antinociceptive, and respiratory-depressant effects of oxycodone in male rats.METHODS:
To determine oxycodone/nalfurafine mixture proportions to be examined intravenously across procedures, a progressive ratio (PR) self-administration procedure compared the reinforcing effects of oxycodone (56 µg/kg/inj) available alone or as a mixture with co-administered nalfurafine (0.32, 1, or 3.2 µg/kg/inj), corresponding to oxycodone/nalfurafine proportions of 1751, 561, and 181, respectively. Next, PR and thermal antinociception dose-effect functions were each determined for oxycodone, nalfurafine, and the same oxycodone/nalfurafine mixture proportions. Finally, the respiratory-depressant effects of equi-antinociceptive doses of oxycodone, nalfurafine, and the mixtures were compared.RESULTS:
Nalfurafine decreased the reinforcing effects of oxycodone, and the 181 mixture did not function as a reinforcer. Oxycodone and nalfurafine each produced dose-dependent antinociception, and the mixtures produced additive antinociception. In addition, antinociceptive doses of the 561 and 181 mixtures did not produce respiratory depression.CONCLUSIONS:
These results suggest that nalfurafine may augment the thermal antinociceptive effects while reducing the reinforcing and respiratory-depressant effects of oxycodone.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxycodone
/
Respiration
/
Spiro Compounds
/
Nociception
/
Analgesics
/
Analgesics, Opioid
/
Morphinans
Limits:
Animals
Language:
En
Journal:
Psychopharmacology (Berl)
Year:
2017
Document type:
Article
Affiliation country:
United States