Discovery of δ Opioid Receptor Full Inverse Agonists and Their Effects on Restraint Stress-Induced Cognitive Impairment in Mice

The cyclopropylmethyl group in classical δ opioid receptor (DOR) antagonist NTI, BNTX, and NTB was replaced with various electron-withdrawing groups to develop DOR inverse agonists. N-Benzyl NTB derivative SYK-657 was a potent DOR full inverse agonist and its potency was over 10-fold potent than tha...

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Bibliographic Details
Published in:ACS chemical neuroscience 2019-05, Vol.10 (5), p.2237-2242
Main Authors: Hirayama, Shigeto, Iwai, Takashi, Higashi, Eika, Nakamura, Minami, Iwamatsu, Chiharu, Itoh, Kennosuke, Nemoto, Toru, Tanabe, Mitsuo, Fujii, Hideaki
Format: Article
Language:English
Subjects:
Analgesics, Opioid - pharmacology
Animals
Behavior, Animal - drug effects
Cognition - drug effects
Cognitive Dysfunction
Drug Inverse Agonism
Male
Memory, Short-Term - drug effects
Mice
Receptors, Opioid, delta - agonists
Restraint, Physical
Stress, Psychological
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Summary:The cyclopropylmethyl group in classical δ opioid receptor (DOR) antagonist NTI, BNTX, and NTB was replaced with various electron-withdrawing groups to develop DOR inverse agonists. N-Benzyl NTB derivative SYK-657 was a potent DOR full inverse agonist and its potency was over 10-fold potent than that of a reference compound ICI-174,864. Intraperitoneal administration of SYK-657 induced the short-term memory improving effect in mice without abnormal behaviors.
ISSN:1948-7193
1948-7193
DOI:10.1021/acschemneuro.9b00067