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Structural and electronic requirements for potent agonists at a nicotinic receptor

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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.

References (10)

  • W.H. Beers et al.

    Structure and activity of acetylcholine

    Nature

    (1970)
  • D. Colquhoun
  • Davies, K., Chemical Design, Ltd., Botley Works, Oxford, OX2 ONN,...
  • A.R. Katrizky

    An attempt to simulate the biogenesis of strychnine. II. Preparation and transformations of 3-(2–4′-pyridylacetamidoethyl) indole

    J. Chem. Soc.

    (1955)
  • N.V. Khromov-Borisov et al.

    Conformation of acetylcholine and its amide analogs during their interaction with nicotinic cholinoreceptors

    Dokl. Acad. Nauk SSSR

    (1976)
There are more references available in the full text version of this article.

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