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ID: ALA4627370
Journal: Bioorg Med Chem Lett
Title: Discovery of δ opioid receptor full agonists lacking a basic nitrogen atom and their antidepressant-like effects.
Authors: Fujii H, Uchida Y, Shibasaki M, Nishida M, Yoshioka T, Kobayashi R, Honjo A, Itoh K, Yamada D, Hirayama S, Saitoh A.
Abstract: We have recently reported that the elaboration of the N-substituent in the δ opioid receptor (DOR) antagonist naltrindole (NTI) enabled the regulation of the DOR activities from full inverse agonists to weak partial agonists. The investigations of amide-type NTI derivatives revealed that N-phenylacetyl and N-dihydrocinnamoyl derivatives 3a and 3b were DOR full agonists. The same transformations were applied to a DOR agonist KNT-127 to provide the more potent DOR agonists 6a and 6b. Among the tested compounds, the most efficacious compound 6a showed dose-dependent antidepressant-like effects in the mouse forced swim test. The antidepressant-like effects by 6a seemed to be more potent than those of KNT-127, which is a more potent DOR agonist in in vitro assays. The amide-type compound like 6a may more fully penetrate into the central nervous system.
CiteXplore: 32299730