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Updated: Dec 17, 2025

Rapid In Situ Hybridization using Oligonucleotide Probes on Paraformaldehyde-prefixed Brain of Rats with Serotonin Syndrome
Published on: September 23, 2015
Discovery of 4-Phenylpiperidine-2-Carboxamide Analogues as Serotonin 5-HT2C Receptor-Positive Allosteric Modulators
Eric A Wold1,2, Erik J Garcia1, Christopher T Wild1,2
1Center for Addiction Research, University of Texas Medical Branch, Galveston, Texas 77555, United States.
Abstract:
Targeting the serotonin (5-HT) 5-HT2C receptor (5-HT2CR) allosteric site to potentiate endogenous 5-HT tone may provide novel therapeutics to alleviate the impact of costly, chronic diseases such as obesity and substance use disorders. Expanding upon our recently described 5-HT2CR-positive allosteric modulators (PAMs) based on the 4-alkylpiperidine-2-carboxamide scaffold, we optimized the undecyl moiety at the 4-position with variations of cyclohexyl- or phenyl-containing fragments to reduce rotatable bonds and lipophilicity. Compound 12 (CTW0415) was discovered as a 5-HT2CR PAM with improved pharmacokinetics and reduced off-target interactions relative to our previous series of molecules. The in vivo efficacy of compound 12 to potentiate the effects of a selective 5-HT2CR agonist was established in a drug discrimination assay. Thus, 12 is reported as a 5-HT2CR PAM with characteristics suitable for in vivo pharmacological studies to further probe the biological and behavioral mechanisms of allosteric modulation of a receptor important in several chronic diseases.
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