Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2002-5-21
pubmed:abstractText
The highly potent synthetic narcotic compound etorphine is known to cause strong analgesia, catatonia and blockade of conditioned reflexes in laboratory animals and is widely used for the immobilisation of game animals. In this study, a number of new structural analogues of etorphine, including C18-beta-structures, 3-O-methylether derivatives and saturated C7-C8 dihydro-compounds, were synthesised and examined in in vitro ligand binding experiments. Opiate receptor-mediated activation of G-proteins by these derivatives was also investigated using the [35S]GTPgammaS binding assay. The receptor binding affinity constant and G-protein stimulatory potency of the novel beta-etorphins were compared with those of the corresponding C18-alpha-derivatives. In rat brain membrane preparations, all the compounds tested displayed high affinity (K(i)'s ranging 0.4-22 nM) using [3H]naloxone in competition assays. The alpha-etorphines had somewhat higher affinity in comparison with the beta-structures. Methylether derivatives were consistently weaker than the corresponding phenolic compounds. Dihydroetorphine and beta-dihydroetorphine, which have a partially saturated ring structure, showed as good potency in the binding assays as did etorphine and beta-etorphine with C7-C8 double bonds. The etorphine derivatives were potent but naloxone-reversible activators of G-proteins in the [35S]GTPgammaS functional tests. It was also found that the C3 phenolic group is favourable for G-protein activation. On the basis of our experimental results, neither the configuration of C18 nor the saturation of the C7-C8 double bond appears to play a critical role in the biological activity of etorphines.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
442
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Biochemical characterisation of newly developed beta-etorphine and beta-dihydroetorphine derivatives.
pubmed:affiliation
Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't