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 language | English (US) |
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Pages (from-to) | 177-185 |
Number of pages | 9 |
Journal | General Pharmacology |
Volume | 12 |
Issue number | 3 |
DOIs | |
State | Published - 1981 |
Externally published | Yes |
ASJC Scopus subject areas
- Pharmacology