Journal
DRUG AND ALCOHOL DEPENDENCE
Volume 121, Issue 3, Pages 181-188Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.drugalcdep.2011.10.026
Keywords
MOP receptors; Herkinorin; beta-Arrestin-2; Morphine; Tolerance; Formalin
Categories
Funding
- NIDA NIH HHS [R01 DA018151-01A2, K01 DA014600-01, R01 DA018860-01, K01 DA014600, R01 DA018151, R13 DA029347, R01 DA018860, R01 DA018151-05S1] Funding Source: Medline
Ask authors/readers for more resources
Herkinorin is the first mu opioid (MOP) selective agonist derived from salvinorin A, a hallucinogenic natural product. Previous work has shown that, unlike other opioids, herkinorin does not promote the recruitment of beta-arrestin-2 to the MOP receptor and does not lead to receptor internalization. This paper presents the first in vivo evaluation of herkinorin's antinociceptive effects in rats, using the formalin test as a model of tonic inflammatory pain. Herkinorin was found to produce a dose-dependent decrease in the number of flinches evoked by formalin. These antinocicepdve effects were substantially blocked by pretreatment with the nonselective antagonist naloxone, indicating that the antinociception is mediated by opioid receptors. Contralateral administration of herkinorin did not attenuate the number of flinches evoked by formalin, indicating that its effects are peripherally restricted to the site of injection. Following chronic administration (5-day), herkinorin maintained antinociceptive efficacy in both phases of the formalin test. Furthermore, unlike morphine, herkinorin was still able to inhibit flinching in both phases of the formalin test in animals made tolerant to chronic systemic morphine treatment. Collectively, these results suggest that herkinorin may produce peripheral antinociception with decreased tolerance liability and thereby represents a promising template for the development of agents for the treatment of a variety of pain states. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available