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The Interpretation of Drug Action through Linear Free Energy Relationships

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Advances in Linear Free Energy Relationships

Abstract

Students of the evaluation of the effects of chemical agents on biological systems have often hoped to be able to predict the biological effect of a given substance from its chemical constitution, or to have methods for the analysis of biological activities, which would provide insight into the mechanism of action of a given drug. In some respects, this possibility might be thought capable of being realised, at least partially, by the application of the same quantum chemical and linear free energy methods which are powerful predictive and analytical tools for the study of chemical reactions. The application of these methods to biological systems, however, must be recognised at the outset to lack, at present, the rigour to which one is accustomed in dealing with chemical systems. With drugs, what is observed in vivo is some biological effect such as an alleviation of pain, a relaxation of muscular or psychological tension, or a reduction in inflammation. Quantification of a drug effect observed in vivo ordinarily provides little information about the details of the processes responsible for the effect. Usually the drug response in vivo is a manifestation of the influence of non-pharmacological events such as absorption, distribution, metabolism, and accumulation or binding, on the processes generating a pharmacological response. Only seldom, and most commonly with in vivo systems, does a drug effect appear to reflect the outcome of a direct combination of the drug with a pharmacological receptor, and even in these instances the characteristics of the drug as to penetration through membranes are not without influence. The events following the combination of drug and receptor, which constitute the pharmacological mechanism leading to the observed biological response, are largely unknown.

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Authors and Affiliations

  1. School of Pharmacy, Temple University, Philadelphia, Pennsylvania, 19140, USA

    Arthur Cammarata

  2. Medical College, Department of Biochemistry, Virginia Commonwealth University, Richmond, Virginia, 23219, USA

    Kenneth S. Rogers

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  1. Arthur Cammarata
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  1. Department of Chemistry, The University, Hull, HU6 7RX, England

    N. B. Chapman  & J. Shorter  & 

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Cammarata, A., Rogers, K.S. (1972). The Interpretation of Drug Action through Linear Free Energy Relationships. In: Chapman, N.B., Shorter, J. (eds) Advances in Linear Free Energy Relationships. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-8660-9_9

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