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Pharmacodynamics: The Interaction of Drugs with Receptors

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Principles in General Pharmacology

Part of the book series: Springer Series in Pharmacologic Science ((SSPHARMACOL))

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Abstract

Drugs with diverse biological actions yield dose-response curves that are rather similar in shape. Whether a drug’s effect is on vascular smooth muscle, the central nervous system, the heart, or some other tissue, the relationship between the observed drug effect and the drug concentration is relatively uniform. The question of why the dose-response curves of diverse agonists appear similar led early theorists to seek a common mechanism by which drugs produce their effects. From this search the existence of specific receptors and the interaction between drug and receptor as a chemical reaction evolved.

The distinction between affinity and intrinsic activity therefore seems of general importance. —E.J. Ariëns, 1954.

The mathematical methods used in bioassays have become so complicated that few pharmacologists can keep track of them. —J.H. Gaddum, 1953

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References

  1. Ariëns EJ: Affinity and intrinsic activity in the theory of competitive inhibition: problems and theory. Arch Int Pharmacodynam 1954;99:32.

    Google Scholar 

  2. Ariëns EJ: Molecular Pharmacology. New York, Academic Press, 1964.

    Google Scholar 

  3. Arunlakshana O, Schild HO: Some quantitative uses of drug antagonists. Br J Pharmacol 1959; 14:48.

    CAS  Google Scholar 

  4. Barlow RB, Scott NC, Stephenson RP: The affinity and efficacy of onium salts on frog rectus abdominus. Br J Pharmacol 1967;31:188.

    CAS  Google Scholar 

  5. Besse JC, Furchgott RF: Dissociation constants and relative efficacies of agonists acting on alpha adrenergic receptors in rabbit aorta. J Pharmacol Exp Ther 1976; 197:66.

    PubMed  CAS  Google Scholar 

  6. Broadley KJ, Nicholson CD: Estimation of dissociation constants and relative efficacies of isoprenaline, orciprenaline and terbutaline in guinea pig isolated atria by use of functional antagonism. Br J Pharmacol 1978;64:420P.

    Google Scholar 

  7. Colquhoun D: in Drug Receptors (HP Rang, ed.) London, Macmillan, 1973.

    Google Scholar 

  8. Changeux JP, Thiery J, Tung Y, Kittel C: On cooperativity of biological membranes. Proc. US Natl Acad Sci 1967;57:335.

    Article  CAS  Google Scholar 

  9. Clark AJ: The Mode of Action of Drugs on Cells. Baltimore, Williams & Wilkins, 1933.

    Google Scholar 

  10. Cope FW: A theory of enzyme kinetics based on electron conduction through the enzymatic particles with applications to cytochrome oxidases and to free radical decay in melanin. Arch Biochem Biophys 1963; 103:352.

    Article  PubMed  CAS  Google Scholar 

  11. Cope FW: I melanin free radical kinetics and mechanism in relation to the Roginski Elovich equation and the adsorption of oxygen by semiconductors. J Chem Physics 1964;440:2653.

    Google Scholar 

  12. Cope FW: A review of the applications of solid state physics concepts to biological systems. J Biol Physics 1975;3:1.

    Article  CAS  Google Scholar 

  13. Cope FW: Derivation of the Weber-Fechner Law and the Lowenstein equation as the steady-state response of an Elovich solid state biological system. Bull Math Biol 1976;38:111.

    PubMed  CAS  Google Scholar 

  14. Czerlinski GH: Chemical Relaxation. New York, Marcel Dekker, 1966.

    Google Scholar 

  15. Ehrlich P: in The Collected Papers of Paul Ehrlich. vol III, Chemotherapy (F. Himmelweit, ed.). London, Pergamon, 1960.

    Google Scholar 

  16. Faller L: Relaxation methods in chemistry. Sci Am, p. 30, 1969.

    Google Scholar 

  17. Furchgott RF: The pharmacological differentiation of adrenergic receptors. Ann NY Acad Sci 1961; 139:553.

    Article  Google Scholar 

  18. Furchgott RF: Pharmacological characterization of receptors: Its relation to radioligand binding studies. Fed Proc 1978;37:115.

    PubMed  CAS  Google Scholar 

  19. Furchgott RF, Bursztyn P: Comparisons of dissociation constants and relative efficacies of selected agonists acting on parasympathetic receptors. Ann NY Acad Sci 1967;144:882.

    Article  CAS  Google Scholar 

  20. Furchgott RF, Ehrreich SJ, Greenblatt E: The photoactivated relaxation of smooth muscle of rabbit aorta. J Gen Physiol 1961;44:499.

    Article  PubMed  CAS  Google Scholar 

  21. Furchgott RF, Jurkiewicz A, Jurkiewicz NF: in Frontiers of Catecholamine Research (E. Usdin and S. Snyder, eds.) New York, Pergamon, p. 295, 1973.

    Google Scholar 

  22. Gaddum JH: The quantitative effects of antagonistic drugs. J Physiol (Lond) 1937;89:7.

    CAS  Google Scholar 

  23. Gaddum JH: Biologic aspects: The antagonism of drugs. Trans Faraday Soc 1943;39:323.

    Article  CAS  Google Scholar 

  24. Gero A: in Drill’s Pharmacology in Medicine, 4th ed. (J.R. Di Palma, ed.) New York, McGraw-Hill, 1971, p. 71.

    Google Scholar 

  25. Gero A: Use of the biological stimulus in determining parameters of drug action and its relationship to the drug effect: A contribution to the theory of drug action. J Theor Biol 1978;74:469.

    Article  PubMed  CAS  Google Scholar 

  26. Gero A, Tallarida RJ: Biological stimulus and drug effect. J Theor Biol 1977;69:265.

    Article  PubMed  CAS  Google Scholar 

  27. Guldberg CM, Waage P: Forhandlinger i Videnskabs i Christiania. Etudes Affi Chem 1864;35:92, 111.

    Google Scholar 

  28. Hill CM, Waight RD, Bardsley WG: Does any enzyme follow the Michaelis-Menten equation? Mol Cell Biol 1977; 15:173.

    CAS  Google Scholar 

  29. Homer LD: Receptor occupation theory of drug responses. J Theor Biol 1967; 17:399.

    Article  PubMed  CAS  Google Scholar 

  30. Jacob LS, Tallarida RJ: Further studies on the action of ultraviolet light on vascular smooth muscle: Effect of partial irreversible receptor blockade. Arch Int Pharmacodyn 1977;225:166.

    PubMed  CAS  Google Scholar 

  31. Jenkinson DH: The antagonism between tubocurarine and substances which depolarize the endplate. J Physiol 1960; 152:309.

    PubMed  CAS  Google Scholar 

  32. Karlin AJ: On the application of a plausible model of allosteric proteins to the receptor for acetylcholine. J Theor Biol 1967; 16:306.

    Article  PubMed  CAS  Google Scholar 

  33. Katz B, Thesleff S: A study of the desensitization produced by acetylcholine at the motor endplate. J Physiol 1957; 138:63.

    PubMed  CAS  Google Scholar 

  34. Kenakin TP, Black JW: The pharmacological classification of practolol and chlorpractolol. Mol Pharmacol 1978; 14:607.

    PubMed  CAS  Google Scholar 

  35. Langley JN: On the physiology of the salivary secretion. J Physiol 1878; 1:339.

    PubMed  CAS  Google Scholar 

  36. Langley JN: On the reaction of cells and nerve endings to certain poisons. J Physiol 1905;33:374.

    PubMed  Google Scholar 

  37. Langmuir J: The constitution and fundamental properties of solids and liquids: I, solids. J Am Chem Soc 1916;38:2221.

    Google Scholar 

  38. MacKay D: How should pA2 and affinity constants for pharmacological competitive antagonists be estimated? J Pharm Pharmacol 1978;30:312.

    Article  PubMed  CAS  Google Scholar 

  39. Monod J, Changeux JP, Jacob J: Allosteric proteins and control systems. J Mol Biol 1963;6:306.

    Article  PubMed  CAS  Google Scholar 

  40. Monod J, Wyman J, Changeux JP: On the nature of allosteric transitions: A plausible model. J Mol Biol 1965;12:88.

    Article  PubMed  CAS  Google Scholar 

  41. Nickerson M: Receptor occupancy and tissue response. Nature 1956; 178:697.

    Article  PubMed  CAS  Google Scholar 

  42. Paton WDM: A theory of drug action based on the rate of drug-receptor combination. Proc R Soc [Biol] 1961;54:21.

    Article  Google Scholar 

  43. Raffa RB, Tallarida RJ: The concept of a changing receptor concentration: Implications for the theory of drug action. J Theor Biol 1985; 115:625.

    Article  PubMed  CAS  Google Scholar 

  44. Schild HO: pA2, a new scale for the measurement of drug antagonists. Br J Pharmacol 1947;2:189.

    CAS  Google Scholar 

  45. Sheys EM, Green RD: A quantitative study of alpha adrenergic receptors in the spleen and aorta of the rabbit. J Pharmacol Exp Ther 1972; 180:317.

    PubMed  CAS  Google Scholar 

  46. Stephenson RP: A modification of receptor theory. Br J Pharmacol 1956; 11:379.

    CAS  Google Scholar 

  47. Stone M, Angus JA: Development of computer-based estimation of pA2 values and associated analysis. J Pharmacol Exp Ther 1978;207:705.

    PubMed  CAS  Google Scholar 

  48. Szabadi E: A theoretical study of two functionally opposite receptor populations. Br J Pharmacol 1975;55:311P.

    Google Scholar 

  49. Takemori AE, Kupferberg J, Miller JW: Quantitative studies of the antagonism of morphine by nalorphine and naloxone. J Pharmacol Exp Ther 1969; 169:39.

    PubMed  CAS  Google Scholar 

  50. Takemori AE, Hyashi G, Smits SE: Studies on the quantitative antagonism of analgesics by naloxone and diprenorphine. Eur J Pharmacol 1972;20:85.

    Article  PubMed  CAS  Google Scholar 

  51. Tallarida RJ, Cowan A, Adler MW: pA2 and receptor differentiation: A statistical analysis of competitive antagonism. Life Sci (minireview) 1979;25:637.

    CAS  Google Scholar 

  52. Tallarida RJ, Laskin O, Jacob LS: Perturbation of drug receptor equilibrium in the presence of competitive blocking agents. J Theor Biol 1976;61:211.

    Article  PubMed  CAS  Google Scholar 

  53. Tallarida RJ, Sevy RW, Harakal C: Relaxation methods for the determination of drug receptor affinities. Bull Math Biophysics 1970;32:65.

    Article  CAS  Google Scholar 

  54. Tallarida RJ, Sevy RW, Harakal C, Loughnane M; Characteristics of photorelaxation in vascular smooth muscle: Evidence supporting the hypothesis of drug-receptor equilibrium disturbance. IEEE Trans Biomed Engineering 1975; 22:493.

    Article  CAS  Google Scholar 

  55. Tallarida RJ, Sevy RW, Harakal C, Bendrick J, Faust R: The effect of preload on the dissociation constant of norepinephrine in isolated strips of rabbit thoracic aorta. Arch Int Pharmacoyn 1974;210:67.

    CAS  Google Scholar 

  56. Tallarida RJ, Raffa RB, Aceto JF: Receptor down regulation, competitive antagonism and pA2. FASEB, April, 1986.

    Google Scholar 

  57. Tallarida RJ, Murray RB: Manual of Pharmacologic Calculation with Computer Programs, 2nd ed., New York, Springer-Verlag, 1987.

    Google Scholar 

  58. Thron CD: On the analysis of pharmacologic experiments in terms of an allosteric receptor model. Mol Pharmacol 1973;9:1.

    PubMed  CAS  Google Scholar 

  59. Waud DR: Pharmacological receptors. Pharmacol Rev 1968;20:49.

    PubMed  CAS  Google Scholar 

  60. Waud DR: On the measurement of affinity of partial agonists for receptors. J Pharmacol Exp Ther 1969;170:117.

    PubMed  CAS  Google Scholar 

  61. Waud DR: in Methods in Pharmacology 3. Smooth Muscle (E.E. Daniel and D.M. Paton, eds.) New York, Plenum, 1975, Chapt. 27.

    Google Scholar 

Additional Readings

  • Colquhoun D: How fast do drugs work? Trends Pharmacol Sci August, 1981.

    Google Scholar 

  • Kenakin TP: The Classification of drugs and drug receptors in isolated tissues. Pharmacol Rev 36:165, 1984.

    PubMed  CAS  Google Scholar 

  • Klotz IM: Numbers of receptor sites from Scatchard graphs: Facts and fantasies. Science 217:24, 1982.

    Article  Google Scholar 

  • Limbird LE: Cell surface receptors: A short course on theory and methods. Martinus Nijhoff, Boston, 1986.

    Google Scholar 

  • Poste G, Crooke ST: (eds.) Mechanisms of receptor regulation. Plenum, New York, 1985.

    Google Scholar 

  • Raffa RB, Tallarida RJ: The concept of a changing receptor concentration: implications for the theory of drug action. J Theor Biol 1985; 115:625.

    Article  PubMed  CAS  Google Scholar 

  • Tallarida RJ, Jacob LS: The dose response relation in pharmacology. Springer-Verlag, New York, 1979.

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania, 19140, USA

    Ronald J. Tallarida Ph.D. (Professor of Pharmacology) & Robert B. Raffa Ph.D. (Senior Scientist, Adjunct Assistant Professor)

  2. Janssen Research Foundation, Spring House, Pennsylvania, 19477, USA

    Robert B. Raffa Ph.D. (Senior Scientist, Adjunct Assistant Professor)

  3. Jefferson Medical College, Philadelphia, Pennsylvania, 19107, USA

    Robert B. Raffa Ph.D. (Senior Scientist, Adjunct Assistant Professor)

  4. Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, USA

    Paul McGonigle Ph.D. (Assistant Professor)

Authors
  1. Ronald J. Tallarida Ph.D.
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  2. Robert B. Raffa Ph.D.
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  3. Paul McGonigle Ph.D.
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© 1988 Springer-Verlag New York Inc.

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Tallarida, R.J., Raffa, R.B., McGonigle, P. (1988). Pharmacodynamics: The Interaction of Drugs with Receptors. In: Principles in General Pharmacology. Springer Series in Pharmacologic Science. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-3778-5_8

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  • DOI: https://doi.org/10.1007/978-1-4612-3778-5_8

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-8346-1

  • Online ISBN: 978-1-4612-3778-5

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