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Cited by 951

The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.

Operational models of pharmacological agonism

Black, James Whyte, Leff, P.·1983·Proceedings of the Royal Society of London. Series B. Biological Sciences
DOI 10.1098/rspb.1983.0093
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Abstract

The traditional receptor-stimulus model of agonism began with a de­scription of drug action based on the law of mass action and has developed by a series of modifications, each accounting for new experimental evidence. By contrast, in this paper an approach to modelling agonism is taken that begins with the observation that experimental agonist-concentration effect, E/[A], curves are commonly hyperbolic and develops using the deduction that the relation between occupancy and effect must be hyperbolic if the law of mass action applies at the agonist-receptor level. The result is a general model that explicity describes agonism by three parameters: an agonist-receptor dissociation constant, KA; the total receptor concentration, [R0]; and a parameter, KE, defining the transduction of agonist-receptor complex, AR, into pharmacological effect. The ratio, [R0]/KE, described here as the ‘transducer ratio’, τ, is a logical definition for the efficacy of an agonist in a system. The model may be extended to account for non-hyperbolic E/[A] curves with no loss of meaning. Analysis shows that an explicit formulation of the traditional receptor-stimulus model is one particular form of the general model but that it is not the simplest. An alternative model is proposed, representing the cognitive and transducer functions of a receptor, that describes agonist action with one fewer parameter than the traditional model. In addition, this model provides a chemical definition of intrinsic efficacy making this parameter experimentally accessible in principle. The alter­native models are compared and contrasted with regard to their practical and conceptual utilities in experimental pharmacology.

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Show all 51 references

Research works printed but not linked: 12

  1. Ariens E. J., 1954, Affinity and intrinsic activity in the theory of competitive inhibition. Archs int, Pharmacodyn. Ther., 99, 32
  2. Ariens E. J., 1956, A theoretical basis of molecular pharmacology, part III, Arzneimittel-Forsch., 6, 737
  3. Clark A. J. 1937 In Handbuch der experimentell Pharmakologie (ed. W. Heubner &J. Schuller). Berlin: Julius Springer.
  4. Dean D. M., 1978, Contribution of adrenergic and " purinergic, J. Pharmacol, exp. Ther., 207, 431
  5. Fuder H., 1981, Alpha adrenoceptors of rabbit aorta and stomach fundus. J. Pharmacol, exp, Ther., 217, 1
  6. Furchgott R. F., 1966, The use of p-haloalkylamines in the differentiation of receptors and in the determination of dissociation constants of receptor-agonist complexes, Adv. Drug Res., 3, 21
  7. Gaddum J. H., 1937, The quantitative effects of antagonistic drugs, J. Physiol. Lond., 89, 7
  8. Gaddum J. H., 1953, Biossays and mathematics, Pharmac. Rev., 5, 87
  9. Mackay D., 1966, a A new method for the analysis of drug-receptor interactions, Adv. Drug Res., 3, 1
  10. Stephenson R. P., 1953, Acetylcholine receptors and alkyltrimethylammonium salts, Abstr. Comm. X IX International Physiol. Congress. Montreal, 801
  11. Triggle D. J., 1980, Desensitization, T. I. P., 395
  12. Waud D. R., 1969, A quantitative model for the effect of a saturable uptake on the slope of the dose-response curve. J. Pharmacol, exp, Ther., 167, 140

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Metadata

Authors
Black, J. W., & Leff, P.
Venue
Proceedings of the Royal Society of London. Series B. Biological Sciences
Publisher
The Royal Society
Published
1983-12-22
Volume
220
Issue
1219
Pages
141-162
ISSN
  • 0080-4649
  • 2053-9193
DOI
10.1098/rspb.1983.0093
Cited by
951
References
51
Language
en
Licence
royalsociety.org/journals/ethics-policies/data-sharing-mining/ (tdm)

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