Conformational analysis of the reverse ester of acetylcholine, cholinergic potency, and cholinergic models

K. W. Reed, W. J. Murray, E. B. Roche, L. N. Domelsmith

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

1. 1. The conformational energy profile of the reverse ester of acetylcholine, a potent nicotinic agonist, was studied using EHT and PCILO molecular orbital calculations. 2. 2. The preferred conformation calculated by EHT has T1 = T2 = 180°, {A figure is presented} which is an extended molecule. 3. 3. The PCILO calculated preferred conformer has T1 = T2 = 60°, which corresponds to a folded molecule. 4. 4. The calculated preferred conformers do not match the preferred conformer given by X-ray crystallography. 5. 5. Comparison of the preferred conformations with the cholinergic potency of the reverse ester reveals that the models developed by Kier and by Chothia & Pauling for muscarinic and nicotinic activity cannot explain the activity of the reverse ester. 6. 6. A model based on the flexibility of the receptors and of the cholinergic molecules and electronic similarities in requisite atomic centers is necessary to explain the activity satisfactorily.

Original languageEnglish (US)
Pages (from-to)177-185
Number of pages9
JournalGeneral Pharmacology
Volume12
Issue number3
DOIs
StatePublished - 1981

ASJC Scopus subject areas

  • Pharmacology

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