Abstract: Provided are embodiments of para-substituted 1,1-dialkyl-4-phenylpiperazin-1-ium iodides advantageous for modulating inflammation that have been synthesized and their electrophysiology activities for ?9, ?9?10, and ?7 nAChRs compared. The para position contained alkyl or aryl amides, or heterocyclic isosteres for the amide, and the alkyl groups were varied at the ammonium piperazine nitrogen to see if compensatory changes in size at this position of the molecule impacted function. The compounds were characterized with two-electrode voltage-clamp measurements on Xenopus oocytes expressing nAChRs. General, the compounds were more potent for ?9-containing receptors than for ?7, and the majority were either full or strong partial agonists for ?9-containing nAChR.

Abstract: Provided are embodiments of para-substituted 1,1-dialkyl-4-phenylpiperazin-1-ium iodides advantageous for modulating inflammation that have been synthesized and their electrophysiology activities for ?9, ?9?10, and ?7 nAChRs compared. The para position contained alkyl or aryl amides, or heterocyclic isosteres for the amide, and the alkyl groups were varied at the ammonium piperazine nitrogen to see if compensatory changes in size at this position of the molecule impacted function. The compounds were characterized with two-electrode voltage-clamp measurements on Xenopus oocytes expressing nAChRs. General, the compounds were more potent for ?9-containing receptors than for ?7, and the majority were either full or strong partial agonists for ?9-containing nAChR.

Abstract: Provided are embodiments of para-substituted 1,1-dialkyl-4-phenylpiperazin-1-ium iodides advantageous for modulating inflammation that have been synthesized and their electrophysiology activities for ?9, ?9?10, and ?7 nAChRs compared. The para position contained alkyl or aryl amides, or heterocyclic isosteres for the amide, and the alkyl groups were varied at the ammonium piperazine nitrogen to see if compensatory changes in size at this position of the molecule impacted function. The compounds were characterized with two-electrode voltage-clamp measurements on Xenopus oocytes expressing nAChRs. General, the compounds were more potent for ?9-containing receptors than for ?7, and the majority were either full or strong partial agonists for ?9-containing nAChR.