Letter | Published:

Effects of L-dopa metabolites at a dopamine receptor suggest a basis for ‘on-off’ effect in Parkinson's disease

Naturevolume 254pages7072 (1975) | Download Citation



ALTHOUGH L-dopa is the most effective therapeutic agent available for the control of the akinesia of Parkinson's disease, long term therapy may be associated with a variety of therapeutic problems1. One problem seen in some patients is a progressive loss of therapeutic response which may be associated with abnormal involuntary movements1. A state may develop in which a good response to the drug alternates with periods of akinesia and rigidity1–4. This has been called the ‘on-off’ effect or akinesia paradoxica1. While low blood levels of L-dopa may explain the onset of akinesia (‘off’ effect), this cannot explain the sudden reversal of patients' akinesia (‘on’ effect) which may occur without additional dosage of L-dopa2,3.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Barbeau, A., Ann. Rev. Pharmac., 14, 91–113 (1974).

  2. 2

    Fahn, S., Neurology, 24 (5), 431–441 (1974).

  3. 3

    Claveria, L. E., Calne, D. B., and Allen, J. G., Br. med. J., 2, 641–643 (1973).

  4. 4

    Cotzias, G. C., Patavasiliou, P. S., Duby, S. E., Steck, A. J., and Ginos, J. Z., Neurology, 22 (5) part 2, 82–85 (1972).

  5. 5

    Hornykiewicz, O., Fedn Proc., 32, 183–190 (1973).

  6. 6

    Sandier, M., Carter, S. B., Hunter, K. R., and Stern, G. M., Nature, 241, 439–443 (1973).

  7. 7

    Turner, A. J., Baker, K. M., Algeri, S., Frigerid, A., and Garattini, S., Life Sci., 14, 2247–2257 (1974).

  8. 8

    Sourkes, T. L., Nature, 229, 413–414 (1971).

  9. 9

    Dougan, D. F. H., and McLean, J. R., Comp. gen. Pharmac., 1, 33–46 (1970).

  10. 10

    Miller, R., Horn, A., and Iversen, L., Nature, 250, 238–241 (1974).

  11. 11

    Sheppard, H., and Burghardt, C., Res. Commun. chem. path. Pharmac., 8, 527–534 (1974).

  12. 12

    Heikkila, R., Cohen, G., and Dembiec, D., J. Pharmac. exp. Ther., 179, 150–258 (1971).

  13. 13

    Teitel, S., O'Brien, R., and Brossi, A., J. med. Chem., 15, 845–846 (1972).

Download references

Author information


  1. Department of Clinical Pharmacology, St Vincent's Hospital, University of New South Wales, Sydney, New South Wales, Australia

    • , DENIS WADE


  1. Search for DON DOUGAN in:

  2. Search for DENIS WADE in:

  3. Search for PETER MEARRICK 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.