Iptakalim as a human nicotinic acetylcholine receptor antagonist

Jun Hu, Kari Lindenberger, Gang Hu, Hai Wang, Ronald J. Lukas, Jie Wu

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Nicotinic acetylcholine receptors (nAChRs) play many critical roles in nervous system function and have been implicated in a variety of diseases. Drugs acting at nAChRs, perhaps in nAChR subtype-selective manners, can be used to dissect receptor function and perhaps as medications. In the present study, we used patch-clamp whole-cell recording and pharmacological manipulations to evaluate effects of iptakalim hydrochloride (Ipt), which is a drug reported to act as an ATP-sensitive potassium (KATP) channel opener, on selected human nAChRs heterologously expressed in the native nAChR-null SH-EP1 human epithelial cell line. Ipt reduced both peak and steadystate whole-cell current amplitudes mediated by human α4β2-nAChRs in response to nicotinic agonists. It also accelerated current decay, caused a decline in apparent efficacy of agonists, and acted in voltage- and use-dependent manners at α4β2-nAChRs. These findings and the inability of Ipt to block radiolabeled epibatidine binding to α4α2-nAChRs suggest a noncompetitive mechanism of antagonism. Other studies discount effects of Ipt on nAChR internalization or involvement of KATP channels in Ipt-induced inhibition of α4β2-nAChR function. By comparison, α7-nAChRs were less sensitive than α4β2-nAChRs to Ipt acting as an antagonist. Thus, α4β2-nAChRs are among the molecular targets of Ipt, which has utility as a tool in functional characterization and pharmacological profiling of nAChRs.

Original languageEnglish (US)
Pages (from-to)914-925
Number of pages12
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number2
StatePublished - Feb 2006
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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