Contribution of mu and delta opioid receptors to the pharmacological profile of kappa opioid receptor subtypes.

D. I. Brissett, Jennifer Whistler, R. M. van Rijn

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Molecular cloning has identified three opioid receptors: mu (MOR), delta (DOR) and kappa (KOR). Yet, cloning of these receptor types has offered little clarification to the diverse pharmacological profiles seen within the growing number of novel opioid ligands, which has led to the proposal of multiple subtypes. In the present study, utilizing in vitro and in vivo methods including the use of opioid receptor knockout mice, we find that certain antinociceptive effects of the KOR-1 and KOR-2 subtype-selective ligands (+)-(5α,7α,8β)-N-Methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-benzene-acetamide (U69, 593) and 4-[(3,4-Dichlorophenyl)acetyl]-3-(1-pyrrolidinylmethyl)-1-piperazine-carboxylic acid methyl ester fumarate (GR89, 696), respectively, are potentiated by antagonism of MOR and DOR receptors. We believe that our findings can be best explained by the existence of KOR-DOR and KOR-MOR heteromers. We only find evidence for the existence of these heteromers in neurons mediating mechanical nociception, but not thermal nociception. These findings have important clinical ramifications as they reveal new drug targets that may provide avenues for more effective pain therapies.

Original languageEnglish (US)
Pages (from-to)327-337
Number of pages11
JournalEuropean journal of pain (London, England)
Issue number3
StatePublished - Mar 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine


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