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Synthesis and characterization of substituted benzoylhydrazones of naloxone
Author(s) -
Ciszewska Grazyna R.,
Ginos James A.,
Charton Marvin,
Standifer Kelly M.,
Brooks Andrew I.,
Brown George P.,
RyanMoro Jennifer P.,
BerzeteiGurske Ilona,
Toll Lawrence,
Pasternak Gavril W.
Publication year - 1996
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199610)24:2<193::aid-syn11>3.0.co;2-#
Subject(s) - affinities , (+) naloxone , kappa , receptor , chemistry , stereochemistry , opioid , binding affinities , κ opioid receptor , opioid receptor , δ opioid receptor , biochemistry , mathematics , geometry
Naloxone benzoylhydrazone (NalBzoH) has proved a valuable tool in the investigation of opioid receptor subtypes. In the present study, we have examined a series of derivatives of NalBzoH in which substitutions have been made on the benzoyl ring. Overall, we see dramatic effects on the binding affinities of derivatives against the various opioid receptor subtypes. Although the range of affinities against the mu receptors is quite modest, ranges of the others vary almost 30‐fold for kappa 3 , 50‐fold for kappa 1 and 100‐fold for delta and kappa 2 binding. Few substituted derivatives display greater affinity than NalBzoH for any of the receptors, except for delta sites where several derivatives have affinities almost tenfold greater than NalBzoH. Along with the wide variations in affinity, the compounds also appear to exhibit widely divergent activities in traditional biosasays. © 1996 Wiley‐Liss, Inc.