Methylpiperidine analog of hemicholinium-3: A selective, high affinity non-competitive inhibitor of sodium dependent choline uptake system

Tapan K. Chatterjee, John P. Long, Joseph G. Cannon, Ranbir K. Bhatnagar

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The potency of hemicholinium-3 (HC-3) and its analogs to inhibit sodium dependent high affinity choline uptake were evaluated in rat striatal synaptosomal preparation. Hemicholinium-3 inhibited sodium dependent high affinity choline uptake (IC50 = 18 nM) while the half molecule of HC-3, HC-15, was inactive. The order of potency for choline uptake inhibition of piperidine substituted HC-3 molecule was as follows: 4-methylpiperidine (A-5 and CA-5) ⋙ HC-3 ≫ unsubstituted piperidines (CA-1 and A-1) ≫ 2- or 3-methylpiperidine (A-2 and A-3) and 4-hydroxypiperidine (A-7). The tertiary amine derivative of 4-methylpiperidine substituted HC-3 (A-4) was nearly 10-fold less potent than its corresponding quaternary derivative (A-5). Choline uptake was inhibited competitively by HC-3 and non-competitively by A-5. The inhibition of choline uptake by A-5 was readily reversible by washing. A-5 did not inhibit the uptake of dopamine and γ-aminobutyric acid. These findings suggest that the N-methyl,4-methylpiperidine analog of HC-3 (A-5) is the most potent of all known inhibitors of sodium dependent high affinity choline uptake and that the inhibition of choline uptake by this compound is mediated through a mechanism distinct from a simple competitive one.

Original languageEnglish (US)
Pages (from-to)241-248
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number3
Publication statusPublished - May 10 1988



  • Choline uptake
  • Hemicholinium-3 analogs
  • Synaptosomes
  • [H]Hemicholinium-3 binding

ASJC Scopus subject areas

  • Pharmacology

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