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      In vitro bioassay as a predictor of in vivo response

      research-article
      Author(s): 1 , 2 ,
      Publication date (Electronic):
      Journal: Theoretical Biology & Medical Modelling
      Publisher: BioMed Central

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          Abstract

          Background

          There is a substantial discrepancy between in vitro and in vivo experiments. The purpose of the present work was development of a theoretical framework to enable improved prediction of in vivo response from in vitro bioassay results.

          Results

          For dose-response curve reaches a plateau in vitro we demonstrated that the in vivo response has only one maximum. For biphasic patterns of biological response in vitro both the bimodal and biphasic in vivo responses might be observed.

          Conclusion

          As the main result of this work we have demonstrated that in vivo responses might be predicted from dose-effect curves measured in vitro.

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          Most cited references24

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          The Pharmacological Basis of Therapeutics

          Robert Handschumaker (1971)
          Article 0 comments Cited 156 times – based on 0 reviews     Review now
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            Acute opioid receptor desensitization and tolerance: is there a link?

            Stephanie Borgland (2001)
            1. Morphine, used long-term for the treatment of pain, results in drug tolerance. The therapeutic benefits, as well as side effects, of morphine are mediated predominantly via activation of mu-opioid receptors. Although the underlying mechanisms for opioid tolerance remains unclear, early adaptive processes, such as acute receptor desensitization and receptor downregulation, have been suggested to be crucial to the development of opioid tolerance. 2. Other neuroadaptations resulting from chronic opioid use include upregulation of the cAMP pathway, an increase in the cAMP response element-binding protein and Fos-related antigens. However, the connection between upregulation of these cellular elements and the mechanism behind the behavioural phenomenon remains unclear. 3. Acute receptor desensitization is thought to occur via uncoupling of the receptor and G-protein, which is followed by internalization of the receptor from the cell membrane. This process occurs after a few minutes of agonist exposure. Receptor-G-protein uncoupling is mediated via phosphorylation of putative sites on the intracellular loops of activated receptors. 4. Acute desensitization and downregulation of receptors both result in a reduction of agonist efficacy. These events occur early in the cascade of cellular adaptation; however, it is uncertain whether these processes contribute to the long-term changes in receptor sensitivity that occur after repeated exposure to opioids. 5. Acute desensitization may, in fact, be a protective mechanism whereby cells adapt to avoid the development of physiological drug tolerance by rapidly attenuating receptor-mediated signalling. Those drugs that do not cause receptor internalization, such as morphine, may have higher propensities to develop tolerance.
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              The Pharmacological Basis of Therapeutics

              C. KLAASSEN, J. G. HARDMAN, L. LIMBIRD … (1996)
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                Author and article information

                Journal
                Journal ID (nlm-ta): Theor Biol Med Model
                Title: Theoretical Biology & Medical Modelling
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1742-4682
                Publication date Collection: 2005
                Publication date (Electronic): 7 February 2005
                Volume: 2
                Page: 3
                Affiliations
                [1 ]Department of Biochemistry, The University of Queensland, Brisbane, Qld 4072, Australia
                [2 ]UNESCO Chair in healthy life for sustainable development, Moscow State University of Medicine and Dentistry, Delegatskay ulitsa, 20/1, 103473, Moscow, Russian Federation
                Article
                Publisher ID: 1742-4682-2-3
                DOI: 10.1186/1742-4682-2-3
                PMC ID: 549212
                PubMed ID: 15698478
                SO-VID: 6ecdd784-a1c4-415c-8943-459ff43322d0
                Copyright © Copyright © 2005 Barnard and Gurevich; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 24 November 2004
                Date accepted : 7 February 2005
                Categories
                Subject: Research

                ScienceOpen disciplines: Quantitative & Systems biology
                Data availability:
                ScienceOpen disciplines: Quantitative & Systems biology

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