Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Correlation between benzodiazepine receptor occupation and anticonvulsant effects of diazepam


The benzodiazepines are potent anticonvulsants for a wide variety of experimental and clinical seizure disorders1,2. The demonstration of saturable, high-affinity and stereospecific binding sites for the benzodiazepines in the mammalian central nervous system suggests the presence of pharmacological receptors mediating the anticonvulsant properties of these compounds3,4. The good correlation between the anticonvulsant potencies of a series of benzodiazepines and their ability to inhibit 3H-diazepam binding in vitro further supports this hypothesis3,4, but evidence for a direct interaction between benzodiazepines and their receptors, and a subsequent inhibition of seizure activity (or elevation of seizure threshold) is lacking5. Recent reports from our laboratory6 and others7 have demonstrated the feasibility of labelling benzodiazepine receptors in vivo following parental administration of tritiated benzodiazepine. This technique permits one to study the relationship between the anticonvulsant activity of the benzodiazepines in vivo and the number of ‘drug-occupied’ receptors in vitro. We now report that there is an excellent correlation between benzodiazepine receptor occupancy by diazepam and protection against pentylenetetrazol-induced seizures. Furthermore, these results demonstrate that only a small fraction of benzodiazepine receptors need be occupied to produce a complete anticonvulsant effect.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout


  1. Randall, L. O., Shallek, W., Sternbach, L. H. & Ning, R. Y. in Psychopharmacological Agents Vol. 3 (ed. Gordon, M.) 175–281 (Academic, New York, 1974).

    Book  Google Scholar 

  2. Browne, T. R. & Penry, J. K. Epilepsia 14, 277–288 (1973).

    Article  CAS  Google Scholar 

  3. Squires, R. F. & Braestrup, C. Nature 266, 732–734 (1977).

    Article  ADS  CAS  Google Scholar 

  4. Mohler, H. & Okada, T. Science 198, 849–851 (1977).

    Article  ADS  CAS  Google Scholar 

  5. Garattini, S., Mussini, E., Marcucci, F. & Guaitani, A. in The Benzodiazepines (eds Garatinni, S. et al.) 75–97 (Raven, New York, 1973).

    Google Scholar 

  6. Williamson, M. J., Paul, S. M. & Skolnick, P. Nature 275, 551–553 (1978).

    Article  ADS  CAS  Google Scholar 

  7. Chang, R. & Snyder, S. Eur. J. Pharmac. 48, 213–218 (1978).

    Article  CAS  Google Scholar 

  8. Skolnick, P., Goodwin, F. K. & Paul, S. M. Archs gen. Psychiat. 36, 78–80 (1979).

    Article  CAS  Google Scholar 

  9. Braestrup, C. & Squires, R. Br. J. Psychiat. 133, 249–260 (1978).

    Article  CAS  Google Scholar 

  10. Cuatrecases, P. A. Rev. Biochem. 43, 169–214 (1974).

    Article  Google Scholar 

  11. Squires, R. et al. Pharmac. Biochem. Behav. 10, 825–830 (1979).

    Article  CAS  Google Scholar 

  12. Skolnick, P. et al. Proc. natn. Acad. Sci. U.S.A. 76, 1515–1518 (1979).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and Permissions

About this article

Cite this article

Paul, S., Syapin, P., Paugh, B. et al. Correlation between benzodiazepine receptor occupation and anticonvulsant effects of diazepam. Nature 281, 688–689 (1979).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


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.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing