Much of the conceptual framework regarding how to study receptor function evolved from pharmacological investigation of drug action. Consequently, the historical account of the development of receptor theory in this chapter, as well as the outline of how to characterize receptors in intact tissues that follows in chapter 2, will emphasize early investigations of drug action rather than, for example, physiological studies of hormone action. However, the reader must keep in mind that “drug” can be defined as any agent that affects living processes. Drugs presumably bind to receptors designed for interaction with endogenous hormones and neurotransmitters. By way of definition, agonist drugs are analogous to endogenous hormones and neurotransmitters, in the sense that they elicit a biological effect, although the effect elicited may be stimulatory or inhibitory. In contrast, antagonist drugs are defined as agents that block receptor-mediated effects elicited by hormones, neurotransmitters, or agonist drugs by competing for receptor occupancy. Antagonists do not appear to have an endogenous counterpart in the strict sense of a competitive inhibitor of receptor occupancy.


Partial Agonist Receptor Occupancy Rate Theory Competitive Antagonism Mutual Antagonism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Albert, A. (1979) Chemotherapy: history and principles. In Selective Toxicity (6th ed.), Chapman and Hall (eds.), John Wiley and Sons, New York, pp. 182–199. (This section of chapter 6 summarized P. Erhlich’s fundamental contributions to chemotherapy and general “receptor” principles.)Google Scholar
  2. Ariëns, E.J. (1954) Affinity and intrinsic activity in the theory of competitive inhibition. Part I. Problems and theory. Arch. Int. Pharmacodyn 99:32–49.PubMedGoogle Scholar
  3. Ariëns, E.J. (1960) Receptor reserve and threshold phenomena I. Theory and experiments with autonomic drugs tested on isolated organs. Arch. Int. Pharmacodyn 127:459–478.PubMedGoogle Scholar
  4. Ariëns, E.J. and de Groot, W.M. (1954) Affinity and intrinsic-activity in the theory of competitive inhibition. III. Homologous decamethonium-derivatives and succinyl-choline-esters. Arch. Int. Pharmacodyn 99:193–205.PubMedGoogle Scholar
  5. Barger, G. and Dale, H.H. (1910) Chemical structure and sympathomimetic action of amines. J. Physiol. 41:19–59.PubMedGoogle Scholar
  6. Bernard, C. (1856) Physiological analysis of the properties of the muscular and nervous system by means of curare. Comptes Rendus Acad. de Sci. 43:825–829. Translated and reprinted in Readings in Pharmacology, L. Shuster (ed.), Little, Brown and Company, Boston, pp. 73–81.Google Scholar
  7. Black, J.W. and Leff, P. (1983) Operational models of pharmacological agonism. Proc. Royal Soc. London B. 220:141–162.CrossRefGoogle Scholar
  8. Changeux, J.-P. and Podleski, T.R. (1968) On the excitability and cooperativity of the electroplax membrane. Proc. Natl. Acad. Sci. USA 59:944–950.PubMedCrossRefGoogle Scholar
  9. Clark, A.J. (1926) The reaction between acetyl choline and muscle cells. J. Physiol. 61:530–546.PubMedGoogle Scholar
  10. Clark, A.J. (1926) The antagonism of acetyl choline by atropine. J. Physiol. 61:547–556.PubMedGoogle Scholar
  11. Clark, A.J. (1927) The reaction between acetyl choline and muscle cells. Part II. J. Physiol. 64:123–143.PubMedGoogle Scholar
  12. Clark, A.J. (1937) General Pharmacology, pp. 61–98, 176–206 and 215–217. Verlag von Julius Springer, Berlin.CrossRefGoogle Scholar
  13. Clark, A.J. and Raventos, J. (1937) The antagonism of acetylcholine and of quarternary ammonium salts. Quant. J. Exp. Physiol. 26:375–392.Google Scholar
  14. Colquhoun, D. (1973) The relation between classical and cooperative models for drug action. In Drug Receptors, H.P. Rang (ed.), University Park, Baltimore, pp. 149–182.Google Scholar
  15. Dale, H.H. (1914) The action of certain esters and ethers of choline, and their relation to muscarine. J. Pharm. Exp. Ther. 6:174–190.Google Scholar
  16. Erhlich, P. (1913) Chemotherapeutics: scientific principles, methods and results. Lancet 2:445–451.Google Scholar
  17. Furchgott, R.F. (1955) The pharmacology of vascular smooth muscle. Pharmacol. Rev. 7:183–235.PubMedGoogle Scholar
  18. Furchgott, R.F. (1964) Receptor mechanisms. Ann. Rev. Pharmacology 4:21–50.CrossRefGoogle Scholar
  19. Furchgott, R.F. and Bhadrakom, S. (1953) Reactions of strips of rabbit aorta to epinephrine, isoproterenol, sodium nitrite and other drugs. J. Pharmacol. Exp. Ther. 108:129–143.PubMedGoogle Scholar
  20. Gaddum, J.H. (1926) The action of adrenalin and ergotamine on the uterus of the rabbit. J. Physiol. 61:141–150.PubMedGoogle Scholar
  21. Gaddum, J.H. (1937) The quantitative effects of antagonistic drugs. J. Physiology 89:7P–9P.Google Scholar
  22. Gaddum, J.H. (1957) Theories of drug antagonism. Pharm. Rev. 9:211–217.PubMedGoogle Scholar
  23. Goldstein, A., Aronow, L. and Kaiman, S.M. (1974) Principles of Drug Action: The Basis of Pharmacology (2nd ed.). New York: John Wiley and Sons, pp. 82–111.Google Scholar
  24. Karlin, A. (1967) On the application of a “plausible model” of allosteric proteins to the receptor of acetylcholine. J. Theoret. Biol. 16:306–320.CrossRefGoogle Scholar
  25. Langley, J.N. (1878) On the physiology of the salivary secretion. Part II. On the mutual antagonism of atropin and pilocarpin, having especial reference to their relations in the submaxillary gland of the cat. J. Physiol 1:339–369.PubMedGoogle Scholar
  26. Langley, J.N. (1909) On the contraction of muscle, chiefly in relation to the presence of “receptive” substances. Part IV. The effect of curare and of some other substances on the nicotine response of the sartorious and gastrocnemius muscles of the frog. J. Physiol 39:235–295.PubMedGoogle Scholar
  27. Monod, J., Wyman, J. and Changeux, J.-P. (1965) On the nature of allosteric transitions: A plausible model. J. Mol. Biol. 12:88–118.PubMedCrossRefGoogle Scholar
  28. Nickerson, M. (1956) Receptor occupancy and tissue response. Nature 78:697–698.CrossRefGoogle Scholar
  29. Paton, W.D.M. (1961) A theory of drug action based on the rate of drug-receptor combination. Proc Royal Soc. B. 154:21–69.CrossRefGoogle Scholar
  30. Stephenson, R.P. (1956) A modification of receptor theory. Br. J. Pharmacology 11:379–393.Google Scholar
  31. Thron, CD. (1973) On the analysis of pharmacological experiments in terms of an allosteric receptor model. Mol. Pharmacol. 9:1–9.PubMedGoogle Scholar
  32. Thron, CD. and Waud, D.R. (1968) The rate of action of atropine. J. Pharm. Exp. Ther. 160:91–105.Google Scholar
  33. Van Rossum, J.M. and Ariëns, E.J. (1962) Receptor reserve and threshold phenomena II. Theories on drug-action and a quantitative approach to spare receptors and threshold values. Arch. Int. Pharmacodyn 136:385–413.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1986

Authors and Affiliations

  • Lee E. Limbird
    • 1
  1. 1.Vanderbilt UniversityNashvilleUSA

Personalised recommendations