Abstract
1 Measurements have been made of the osmotic coefficients and enthalpies of dilution of acetylcholine and of compounds related to it in which the carbonyl and ether groups have been replaced by methylene and the trimethylammonium group by triethylammonium. All were iodides. Measurements were also made with tetraethylammonium iodide and agree with published values.
2 Where necessary the affinities of the compounds for acetylcholine receptors in the guinea-pig ileum and frog rectus, or their activities relative to acetylcholine, have been measured.
3 The osmotic coefficients were used to calculate activity coefficients and excess free energies, which have been used with the excess enthalpies to calculate the excess entropies of the solutions. These indicate that the ester and carbonyl groups have a marked ordering effect on the ions in water compared with methylene groups; the ether group has an intermediate effect.
4 When the results are interpreted in terms of ion-pair formation they can be used to calculate the ion-association constants and enthalpies and entropies of formation of ion-pairs, and lead to similar conclusions: that the order associated with ion-pair formation is greater with the esters and ketones. There appears to be extensive ion-association in the concentrations (0.5 to 1M) usually used in n.m.r. studies.
5 There is no obvious correlation between the effects of groups on water and their activity or affinity at muscarine-sensitive acetylcholine receptors but it is possible that ability to activate nicotine-sensitive receptors may be associated with an increase in order, though it would be necessary to study entropy changes in systems actually involving receptors in order to prove this. It is also necessary to suppose that ability to activate these receptors is limited to compounds with small onium groups.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abramson F. B., Barlow R. B., Mustafa M. G., Stephenson R. P. Relationships between chemical structure and affinity for acetylcholine receptors. Br J Pharmacol. 1969 Sep;37(1):207–233. doi: 10.1111/j.1476-5381.1969.tb09539.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barlow R. B., Lowe B. M., Pearson J. D., Rendall H. M., Thompson G. M. Ion size and activity at acetylcholine receptors. Mol Pharmacol. 1971 Jul;7(4):357–366. [PubMed] [Google Scholar]
- Barlow R. B., Scott N. C., Stephenson R. P. The affinity and efficacy of onium salts on the frog rectus abdominis. Br J Pharmacol Chemother. 1967 Sep;31(1):188–196. doi: 10.1111/j.1476-5381.1967.tb01989.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barlow R. B., Thompson G. M., Scott N. C. The affinity and activity of compounds related to nicotine on the rectus abdominis muscle of the frog (Rana pipiens). Br J Pharmacol. 1969 Nov;37(3):555–584. doi: 10.1111/j.1476-5381.1969.tb08496.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- ING H. R., KORDIK P., WILLIAMS D. P. H. T. Studies on the structure-action relationships of the choline group. Br J Pharmacol Chemother. 1952 Mar;7(1):103–116. doi: 10.1111/j.1476-5381.1952.tb00696.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kier L. B. A molecular orbital calculation of the preferred conformation of nicotine. Mol Pharmacol. 1968 Jan;4(1):70–76. [PubMed] [Google Scholar]
- Kier L. B. Molecular orbital calculation of preferred conformations of acetylcholine, muscarine, and muscarone. Mol Pharmacol. 1967 Sep;3(5):487–494. [PubMed] [Google Scholar]
- Partington P., Feeney J., Burgen A. S. The conformation of acetylcholine and related compounds in aqueous solution as studied by nuclear magnetic resonance spectroscopy. Mol Pharmacol. 1972 May;8(3):269–277. [PubMed] [Google Scholar]
- Pullman B., Courrière P. Further molecular orbital studies on the conformation of acetylcholine and its derivatives. Mol Pharmacol. 1972 Nov;8(6):612–622. [PubMed] [Google Scholar]
- WELSH J. H., TAUB R. The significance of the carbonyl group and ether oxygen in the reaction of acetylcholine with receptor substance. J Pharmacol Exp Ther. 1951 Sep;103(1):62–73. [PubMed] [Google Scholar]