Smooth Muscle pp 471-506 | Cite as

Analysis of Dose—Response Curves

  • D. R. Waud


The central theme of this chapter will be a consideration of what information can be obtained from analysis of dose-response curves. Generally, as the extent to which one can make mechanistic interpretations increases, so, too, does the degree of caution that should be associated with the interpretation. At one extreme we have a purely empirical measurement such as a determination of the relation between dose and effect. One can simply say that this is what was found and the result is a matter of fact. On the other hand, if the why of it is raised, one can attempt a more mechanistic analysis, but only at the expense of introducing assumptions such that the argument becomes less rigorous. Thus, one tends to seek a middle ground. If possible, the experiment is designed so that not only can it yield empirical information but also shed light on mechanisms. It is often also possible to examine the same experimental results with different underlying models in mind. Thus, one objective of this chapter will be to indicate how best to approach analysis of dose—response curves so that the results may be interpreted as widely as possible.


Dissociation Constant Initial Estimate Normal Equation Longitudinal Muscle Competitive Antagonist 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arunlakshana, O. and Schild, H. O. 1959. Some quantitative uses of drug antagonists. Br. J. Pharmacol, 14:48–58.Google Scholar
  2. Barlow, R. B., Scott, N. C., and Stephenson, R. P. 1967. The affinity and efficacy of onium salts on the frog rectus abdominis. Br. J. Pharmacol., 31:188–196.Google Scholar
  3. Blinks, J. R. 1967. Evaluation of the cardiac effects of several beta adrenergic blocking agents. Ann. N. Y. Acad. Scl, 139:673–685.CrossRefGoogle Scholar
  4. Changeux, J.-P. and Podleski, T. R. 1968. On the excitability and cooperativity of the electroplax membrane. Proc. Nat. Acad. Sci., 59:944–950.PubMedCrossRefGoogle Scholar
  5. Furchgott, R. F. 1955. The pharmacology of vascular smooth muscle. Pharmacol. Rev., 7:183–265.PubMedGoogle Scholar
  6. Furchgott, R. F. and Bursztyn, P. 1967. Comparison of dissociation constants and of relative efficacies of selected agonists acting on parasympathetic receptors. Ann. N.Y. Acad. Sci., 144:882–898.CrossRefGoogle Scholar
  7. Gaddum, J. H., Hameed, K. A., Hathway, D. E., and Stephens, F. F. 1955. Quantitative studies of antagonists for 5-hydroxytryptamine. Quart. J. Exp. Physiol., 40:49–74.PubMedGoogle Scholar
  8. Jenkinson, D. H. 1960. The antagonism between tubocurarine and substances which depolarize the motor end-plate. J. Physiol, 152:309–324.PubMedGoogle Scholar
  9. Karlin, A. 1967. On the application of “a plausible model” of allosteric proteins to the receptor for acetylcholine. J. Theor. Biol,16:306–320.PubMedCrossRefGoogle Scholar
  10. Katz, B. and Thesleff, S. 1957. A study of the “desensitization”produced by acetylcholine at the motor end-plate. J. Physiol, 138:63–80.PubMedGoogle Scholar
  11. Parker, R. B. 1972. Measurement of drug-receptor dissociation constants of muscarinic agonists on intestinal smooth muscle. J. Pharmacol Exp. Ther., 180:62–70PubMedGoogle Scholar
  12. Parker, R. B. and Waud, D. R. 1971. Pharmacological estimation of drug-receptor dissociation constants. Statistical evaluation. 1. Agonists. J. Pharmacol Exp. Ther., 177:1–12.PubMedGoogle Scholar
  13. Paton, W. D. M. and Rang, H. P. 1965. The uptake of atropine and related drugs by intestinal smooth muscle of the guinea pig in relation to acetylcholine receptors. Proc. R. Soc. B, 163:1–44.CrossRefGoogle Scholar
  14. Rang, H. P. and Ritter, J. M. 1969. A new kind of drug antagonism: Evidence that agonists cause a molecular change in acetylcholine receptors. Mol Pharmacol,5:394–411.PubMedGoogle Scholar
  15. Rang, H. P. and Ritter, J. M. 1970a. On the mechanism of desensitization at cholinergic receptors. Mol Pharmacol, 6:383–390PubMedGoogle Scholar
  16. Rang, H. P. and Ritter, J. M. 1970b. The relationship between desensitization and the metaphilic effect at cholinergic receptors. Mol Pharmacol,6:383–390.PubMedGoogle Scholar
  17. Schild, H. O.1947. pA, a new scale for the measurement of drug antagonism. Br. J. Pharmacol, 2:189–206.Google Scholar
  18. Snedecor, G. W. and Cochran, W. G. 1968. Statistical Methods,6th ed. Iowa State University Press, Ames, Iowa.Google Scholar
  19. Stephenson, R. P. 1956. A modification of receptor theory. Br. J. Pharmacol,11:379–393.Google Scholar
  20. Taylor, D. B., Steinborn, J., and Lu, T. 1970. Ion exchange processes at the neuromuscular junction of voluntary muscle. J. Pharmacol Exp. Ther., 175:213–227.PubMedGoogle Scholar
  21. Waud, D. R. 1969. On the measurement of the affinity of partial agonists for receptors, J. Pharmacol Exp. Ther., 175:117–122Google Scholar
  22. Waud, D. R. 1972. On biological assays involving quantal responses.J. Pharmacol Exp. Ther., 183:577–607.PubMedGoogle Scholar
  23. Waud, D. R. and Parker, R. B. 1971. Pharmacological estimation of drug-receptor dissociation constants. Statistical evaluation. II. Competitive antagonists. J. Pharmacol Exp. Ther., 177:13–24PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1975

Authors and Affiliations

  • D. R. Waud
    • 1
  1. 1.Department of PharmacologyUniversity of Massachusetts Medical SchoolWorcesterUSA

Personalised recommendations