A Methyl Scan of the Pyrrolidinium Ring of Nicotine Reveals Significant Differences in Its Interactions with α7 and α4β2 Nicotinic Acetylcholine Receptors.

ABSTRACT: The two major nicotinic acetylcholine receptors (nAChRs) in the brain are the α4β2 and α7 subtypes. A "methyl scan" of the pyrrolidinium ring was used to detect differences in nicotine's interactions with these two receptors. Each methylnicotine was investigated using voltage-clamp and radioligand binding techniques. Methylation at each ring carbon elicited unique changes in nicotine's receptor interactions. Replacing the 1'-N-methyl with an ethyl group or adding a second 1'-N-methyl group significantly reduced interaction with α4β2 but not α7 receptors. The 2'-methylation uniquely enhanced binding and agonist potency at α7 receptors. Although 3'- and 5'-trans-methylations were much better tolerated by α7 receptors than α4β2 receptors, 4'-methylation decreased potency and efficacy at α7 re

SUBMITTER: Xing H 

PROVIDER: S-EPMC7377336 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature