Structural and electronic requirements for potent agonists at a nicotinic receptor

C. E. Spivak, T. M. Gund, R. F. Liang, J. A. Waters

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

A new agonist, isoarecolone methiodide (1,1-dimethyl-4-acetyl-1,2,3,6-tetrahydropyridinium iodide) was tested at the frog neuromuscular junction. It was 50 times more potent than carbamylcholine, making it one of the most potent nicotinic agonists known. In addition, its cyclic structure and conjugated carbonyl bond endow it with near rigidity. An analogous compound, 1,1-dimethyl-4-acetylpiperazinium iodide, was synthesized because of its similar geometry and rigidity. It was 2.6 times as potent as carbamylcholine but only 0.053 times as potent as isoarecolone methiodide. Computer assisted molecular modeling and molecular orbital calculations revealed steric and electrostatic field differences between these two compounds.

Original languageEnglish (US)
Pages (from-to)127-131
Number of pages5
JournalEuropean Journal of Pharmacology
Volume120
Issue number1
DOIs
StatePublished - Jan 14 1986
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology

Keywords

  • Isoarecolone methiodide
  • Molecular modeling
  • Neuromuscular junction
  • Nicotinic receptor

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