Abstract
The study of kappa-opioid receptor function in vivo has been hampered by the limited choice of selective kappa-antagonists. Recently discovered kappa-antagonists have not yet been utilised in vivo. We here report the synthesis and in vitro evaluation of a new amidine derivative of naltrindole. It showed substantially greater kappa-selectivity in binding assays than known analogues with shorter spacer in the amidine side chain. This indicates that in nor-BNI and related selective kappa-antagonists, the second basic centre may not be ideally located.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amidines / chemical synthesis*
-
Amidines / chemistry
-
Amidines / pharmacology
-
Animals
-
Benzeneacetamides*
-
Binding, Competitive
-
Brain / metabolism
-
Cell Membrane / metabolism
-
Drug Design
-
Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacokinetics
-
Enkephalin, D-Penicillamine (2,5)- / pharmacokinetics
-
Guinea Pigs
-
Indicators and Reagents
-
Kinetics
-
Naltrexone / analogs & derivatives*
-
Naltrexone / chemical synthesis
-
Naltrexone / chemistry
-
Naltrexone / pharmacology
-
Narcotic Antagonists / chemical synthesis*
-
Narcotic Antagonists / chemistry
-
Narcotic Antagonists / pharmacology
-
Pyrrolidines / pharmacokinetics
-
Receptors, Opioid, kappa / antagonists & inhibitors*
-
Structure-Activity Relationship
Substances
-
Amidines
-
Benzeneacetamides
-
Indicators and Reagents
-
Narcotic Antagonists
-
Pyrrolidines
-
Receptors, Opioid, kappa
-
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
-
Naltrexone
-
Enkephalin, D-Penicillamine (2,5)-
-
naltrindole
-
U 69593