Synthesis and characterization of substituted benzoylhydrazones of naloxone

✍ Scribed by Grazyna R. Ciszewska; James A. Ginos; Marvin Charton; Kelly M. Standifer; Andrew I. Brooks; George P. Brown; Jennifer P. Ryan-Moro; Ilona Berzetei-Gurske; Lawrence Toll; Gavril W. Pasternak

• Book ID: 102656761
• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 887 KB
• Volume: 24
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(199610)24:2<193::aid-syn11>3.0.co;2-#

✦ Synopsis

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,, 50-fold for kappal and 100-fold for delta and kappaa 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 bioassays.