Stereoselectivity of Some Muscarinic and Antimuscarinic Agents Related to Oxotremorine
Oxotremorine, N-(4-pyrrolidino-2-butynyl)-2-pyrrolidone (), is a muscarinic agent equal in potency to acetylcholine (3, 7). Its extraordinary potency is surprising in view of its structural dissimilarity to other muscarinic agents. Whereas most powerful muscarinic agents possess a quaternary trimethyl ammonium group, oxotremorine is a tertiary amine with no N-methyl groups at all. Moreover, it contains an acetylenic bond at the position in the molecule where strong muscarinic agents have an oxygen atom. The structural requirements for muscarinic activity are rather specific and even slight changes in the structure lead to loss of the muscarinic activity or to a change of the type of activity from agonistic to antagonistic (4, 14). The only amino congeners which show agonistic activity of the same order of magnitude as oxotremorine are the dimethylamino () and the azetidino () analogs. Compound  is in fact the most potent tertiary muscarinic agent known to date (see structures on next page).
KeywordsTertiary Amine Pharmacological Data Pyrrolidine Ring Opposite Configuration Agonist Binding Site
Unable to display preview. Download preview PDF.
- 1.Ariens, E.J. (1966): Advan. Drug Res. 3: 235–285.Google Scholar
- 2.Bebbington, A., Brimblecombe, R.W. and Shakeshaft, D. (1966): Brit. J. Pharmacol. 26: 56–67.Google Scholar
- 3.Cho, A.K., Haslett, W.L. and Jenden, D.J. (1962): J. Pharmacol. Exp. Ther. 138: 249–257.Google Scholar
- 4.Dahlbom, R. (1981): In Cholinergic Mechanisms: Phylogenetic Aspects. Central and Peripheral Synapses, and Clinical Significance (eds) G. Pepeu and H. Ladinsky, Plenum Press, New York, pp. 621–638.Google Scholar
- 5.Dahlbom, R., Jenden, D.J., Resul, B. and Ringdahl, B. (1982): Brit. J. Pharmacol. 76: 299–304.Google Scholar
- 9.Resul, B., Dahlbom, R., Ringdahl, B. and Jenden, D.J. (1982): Eur. J. Med. Chem. 17: 317–322.Google Scholar
- 11.Ringdahl, B. and Dahlbom, R. (1978): Acta Pharm. Suec. 15: 255263.Google Scholar
- 12.Ringdahl, B. and Dahlbom, R. (1979): Acta Pharm. Suec. 16: 13–20.Google Scholar
- 13.Ringdahl,B. and Jenden,D.J. (1983): Mol. Pharmacol. 23: 17–25.Google Scholar