N-Skatyltryptamines-Dual 5-HT₆R/D₂R Ligands with Antipsychotic and Procognitive Potential.

ABSTRACT: A series of N-skatyltryptamines was synthesized and their affinities for serotonin and dopamine receptors were determined. Compounds exhibited activity toward 5-HT_1A, 5-HT_2A, 5-HT₆, and D₂ receptors. Substitution patterns resulting in affinity/activity switches were identified and studied using homology modeling. Chosen hits were screened to determine their metabolism, permeability, hepatotoxicity, and CYP inhibition. Several D₂ receptor antagonists with additional 5-HT₆R antagonist and agonist properties were identified. The former combination resembled known antipsychotic agents, while the latter was particularly interesting due to the fact that it has not been studied before. Selective 5-HT₆R antagonists

SUBMITTER: Hogendorf A 

PROVIDER: S-EPMC8347595 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature