Letter | Published:

Stereoselective blockade of the dopamine receptor and the X-ray structures of α and β-flupenthixol

Naturevolume 256pages342343 (1975) | Download Citation



THE introduction of neuroleptics of the phenothiazine and thioxanthene classes has revolutionised the treatment of schizophrenia and there is increasing evidence1–3 that links this antipsychotic action to a blockade of dopamine receptors in the brain. The thioxanthene compounds are of particular interest as, because of the presence of an exocyclic double bond and a substituent in the tricyclic nucleus, they exist as cis–trans geometric isomers about the double bond with respect to the ring substituent (Fig. 1). Virtually all the neuroleptic activity is confined to the cis isomer4.


  1. 1

    Horn, A. S., and Snyder, S. H., Proc. natn. Acad. Sci U.S.A., 68, 2325–2328 (1971).

  2. 2

    Matthysse, S., Fedn Proc., 32, 200–205 (1973).

  3. 3

    Snyder, S. H., Banerjee, S. P., Yamamura, H. I., and Greenburg, D., Science, 184, 1243–1253 (1974).

  4. 4

    Moller-Nielsen, C. G., et al., Acta pharmac. tox., 33, 353–362 (1973).

  5. 5

    Gottfries, C. G., Br. J. Psychiat., 119, 547–548 (1971).

  6. 6

    Miller, R. J., Horn, A. S., and Iversen, L. L., Mol. Pharmac., 10, 759–766 (1974).

  7. 7

    Horn, A. S., Post, M. L., and Kennard, O., J. Pharm. Pharmac. (in the press).

  8. 8

    Miller, R. J., Horn, A. S., and Iversen, L. L., J. Pharm. Pharmac., 27, 212–213 (1975).

  9. 9

    Bruderlein, F. T., Humber, L. G., and Voith, K., J. med. Chem., 18, 185–188 (1975).

  10. 10

    York, D. H., Brain Res., 37, 91–99 (1972).

  11. 11

    Clement-Cormier, Y. C., Kebebian, J. W., Petzold, G. L., and Greengard, P., Proc. natn. Acad. Sci. U.S.A., 71, 1113–1117 (1974).

  12. 12

    Post, M. L., Kennard, O., and Horn, A. S., Acta crystallogr. B 30, 1644–1646 (1974).

Download references

Author information


  1. University Chemical Laboratory, Lensfield Road, Cambridge, CB2 1EW, UK

  2. Neurochemical Pharmacology Unit, Department of Pharmacology, Medical School, Hills Road, Cambridge, UK

    • ALAN S. HORN


  1. Search for MICHAEL L. POST in:

  2. Search for OLGA KENNARD in:

  3. Search for ALAN S. HORN in:

About this article

Publication history



Issue Date



Further reading


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.