Design, Synthesis, and Characterization of 4-Undecylpiperidine-2-carboxamides as Positive Allosteric Modulators of the Serotonin (5-HT) 5-HT_2C Receptor.

ABSTRACT: An impaired signaling capacity of the serotonin (5-HT) 5-HT_2C receptor (5-HT_2CR) has been implicated in the neurobehavioral processes that promote relapse vulnerability in cocaine use disorder (CUD). Restoration of the diminished 5-HT_2CR signaling through positive allosteric modulation presents a novel therapeutic approach. Several new molecules with the 4-alkylpiperidine-2-carboxamide scaffold were designed, synthesized, and pharmacologically evaluated, leading to the discovery of selective 5-HT_2CR positive allosteric modulators (PAMs). Compound 16 (CYD-1-79) potentiated 5-HT-evoked intracellular calcium release in cells stably expressing the human 5-HT_2CR but not the 5-HT_2AR cells. A topographically distinct allosteric sit

SUBMITTER: Wild CT 

PROVIDER: S-EPMC6533912 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature