Stereoisomers of Chiral Methyl-Substituted Symmetric and Asymmetric Aryl Piperazinium Compounds Exhibit Distinct Selectivity for α9 and α7 Nicotinic Acetylcholine Receptors.

ABSTRACT: We have characterized families of phenylpiperazine (PP) compounds, studying their relative activity with α7 and α9* nicotinic acetylcholine receptors (nAChRs) and focusing on the effects of side groups on the phenyl ring (R₁) and the effects of different alkyl groups on the base nitrogen. In this study, we evaluated the impact of methyl substitution on the piperazine ring, which introduced a chiral center, enabling the generation and separation of stereoisomers. Methyl groups were added to either the C2 or C3 positions on the piperazine of the α9α10 agonist/α7 partial agonist PA-EMPP. Additions at the C3 position greatly reduced activity, while additions at the C2 position had selective effects on either α7 or α9/α10 activity. The 2-methyl S and R isomers of PA-EMP

SUBMITTER: Andleeb H 

PROVIDER: S-EPMC12272543 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature