A highly selective kappa-opioid receptor agonist with low addictive potential and dependence liability.
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.
Park
Hee Sock
HS
Department of Chemistry, KAIST, Daejeon 305-701, Republic of Korea.
Lee
Hee Yoon
HY
Kim
Yong Hae
YH
Park
Jin Kyu
JK
Zvartau
Edwin E
EE
Lee
Heeseung
H
D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy; D001665:Binding Sites; D002047:Buprenorphine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000819:agonists / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D017473:Receptors, Opioid, kappa; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002047:Buprenorphine