Structure Activity Relationships of some Muscarinic Agonists: a Reply to Shefter and Triggle

Article metrics

Abstract

IN essence, the criticism by Shefter and Triggle1 of my model2 for the interaction of acetylcholine, (CH3)3N+-CH2CH2OCOCH3, with muscarinic receptors is that it does not explain the muscarinic potency of some analogues of acetylcholine. I believe that my model does quite simply account for the activity of these compounds. As background information for my model, I made the general statement that muscarinic agonists are observed to have the N+–C–C–O torsion angle between the positive synclinal and positive anticlinal2 (Fig. 1a). Shefter and Triggle do not quote any potent agonists for which this observation is untrue and I briefly show how it can be used to explain the muscarinic activity of the compounds they mention.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Shefter, E., and Triggle, D. J., Nature, 227, 1354 (1970).

  2. 2

    Chothia, C. H., Nature, 225, 36 (1970).

  3. 3

    Scott, K. A., and Mautner, H. G., Biochem. Pharmacol., 13, 907 (1964).

  4. 4

    Shefter, E., Mautner, H. G., and Smissman, E. E., Acta Cryst., A 25, S201 (1969).

  5. 5

    Shefter, E., and Kennard, O., Science, 153, 1389 (1966).

  6. 6

    Smissman, E. E., Nelson, W. L., La Pidus, J. B., and Day, J. L., J. Med. Chem., 9, 458 (1966).

  7. 7

    Beckett, A. H., Harper, N. J., Clitherow, J. W., and Lesser, E., Nature, 189, 671 (1961).

  8. 8

    Triggle, D. J., Chemical Aspects of the Autonomic Nervous System, 83 (Academic Press, London and New York, 1965).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

CHOTHIA, C. Structure Activity Relationships of some Muscarinic Agonists: a Reply to Shefter and Triggle. Nature 227, 1355–1356 (1970) doi:10.1038/2271355a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.