A highly selective kappa-opioid receptor agonist with low addictive potential and dependence liability

Hee Sock Park; Hee Yoon Lee; Yong Hae Kim; Jin Kyu Park; Edwin E Zvartau; Heeseung Lee

doi:10.1016/j.bmcl.2006.02.017

A highly selective kappa-opioid receptor agonist with low addictive potential and dependence liability

Bioorg Med Chem Lett. 2006 Jul 1;16(13):3609-13. doi: 10.1016/j.bmcl.2006.02.017. Epub 2006 May 2.

Authors

Hee Sock Park¹, Hee Yoon Lee, Yong Hae Kim, Jin Kyu Park, Edwin E Zvartau, Heeseung Lee

Affiliation

¹ Department of Chemistry, KAIST, Daejeon 305-701, Republic of Korea.

PMID: 16650985
DOI: 10.1016/j.bmcl.2006.02.017

Abstract

Buprenorphine analogs have been synthesized. In the studies of analgesic and addictive effects in mice and [(35)S]GTPgammaS binding assay in human brain tissue, an analog of buprenorphine where the tert-butyl is replaced by a cyclobutyl moiety (16) has been identified as a selective kappa-partial agonist which gives antinociceptive effects, but has low abuse potential. The results may lead to lower degrees of dysphoria than full kappa-agonists.

MeSH terms

Animals
Behavior, Addictive / drug therapy
Binding Sites
Buprenorphine / analogs & derivatives*
Buprenorphine / chemical synthesis
Buprenorphine / pharmacology*
Cerebral Cortex / drug effects
Drug Evaluation, Preclinical
Guanosine 5'-O-(3-Thiotriphosphate) / agonists
Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
Humans
In Vitro Techniques
Male
Mice
Mice, Inbred Strains
Molecular Structure
Receptors, Opioid, kappa / agonists*
Stereoisomerism
Structure-Activity Relationship

Substances

Receptors, Opioid, kappa
Guanosine 5'-O-(3-Thiotriphosphate)
Buprenorphine