Skip to main content
Log in

Optimization of a Mixture of an Agonist and an Antagonist of the GABA-Receptor System According to the Safety Criterion

  • Published:
Neurophysiology Aims and scope

Abstract

Based on the interaction between various types of pharmacologically active substances, equations of general form were derived that enable us to optimize an agonist-antagonist mixture on the criterion of the maximum safety of application, i.e., the therapeutic index. The character of changes of the therapeutic index of a mixture of pharmacologically active substances is shown depending on the ratio of components in the mixture and the parameters of their elimination. The practical applicability of the dependences derived is shown on the example of the interaction of the effects of the ligands of the GABAA-receptor system: pentylenetetrazole and ethanol.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. X. Xiberas, J. L. Martinot, L. Mallet, et al., “Extrastriatal and striatal D(2) dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia,” Br. J. Psychiat., 179, 503–508 (2001).

    Google Scholar 

  2. R. J. Tallarida, “Receptor discrimination and control of agonist-antagonist binding,” Am. J. Physiol., No. 8, 379–391 (1995).

  3. R. R. Ruffolo, “Fundamentals of receptor theory: basics for shock research,” Circus Shock, June, 176–184 (1992).

  4. B. S. Pallota, “Single ion channel's view of classical receptor theory,” FASEB J. No. 4, 2035–2043 (1991).

    Google Scholar 

  5. D. Hoyer and H. W. Boddeke, “Partial agonists, full agonists, antagonists: dilemmas of definition,” Trends Pharmacol. Sci., No. 3, 270–275 (1993).

    Google Scholar 

  6. V. Petkov, Drug. Organism. Pharmacological Effect [Russian translation], Meditsina Fizkultura, Sofia, Bulgaria (1977).

    Google Scholar 

  7. S. O. Sylantyev, M. S. Zhuk, V. G. Zinkovsky, and M. Ya. Golovenko, “Isodynamic analysis of the manifestations of physiological antagonism and competitive and allosteric interactions of the effects of ligands of the CNS transmitter systems,” Fiziol. Zh., 44,No. 3, 13–17 (1998).

    Google Scholar 

  8. A. Cornish-Bowden, Basic Mathematics for Biochemists, Chapman and Hall, London, New York (1980).

    Google Scholar 

  9. A. Cornish-Bowden, Principles of Enzyme Kinetics, Butterworth, London (1975).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. Sylantyev.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sylantyev, S., Zinkovsky, V. Optimization of a Mixture of an Agonist and an Antagonist of the GABA-Receptor System According to the Safety Criterion. Neurophysiology 34, 243–246 (2002). https://doi.org/10.1023/A:1020744525973

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1020744525973

Navigation