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Schroder, W., Tzschentke, T.M., Terlinden, R., De Vry, J., Jahnel, U., Christoph, T. and Tallarida, R.J. (2011) Synergistic interaction between the two mechanisms of action of tapentadol in analgesia. The Journal of Pharmacology and Experimental Therapeutics, 337, 312-320. doi:10.1124/jpet.110.175042

has been cited by the following article:

• TITLE: Theory of pleiotropic action of biologically active compounds and medicines—Basic principles and practical application

  AUTHORS: N. A. Bizunok

  KEYWORDS: Reactive Oxygen Species (ROS);Nox2-NAD(P)H Oxidase (Nox2); Slope Angles of Dose-Effect Dependences; Pleiotropy; Pleiotropic Patterns; Polytropism; Pharmacological Affect Nature;Medicines Combinations; Novel Theory of Biologically; Active Compounds (BACs) and Medicines Action

  JOURNAL NAME: Open Journal of Clinical Diagnostics, Vol.3 No.3, September 25, 2013

  ABSTRACT: This article represents the main positions of the theory of pleiotropic action of biologically active compounds (BACs) and medicines, which has been designed by the author based on her own experimental researches. The term “pleiotropy” means the ability of the BACs and medicines to implement more than one mechanism of action resulting in the specific biological (pharmacological) effect. The interaction of these mechanisms forms a distinct pattern of biological response (pleiotropic pattern), which reflects the change in his character with the increased dose (concentration)-dependent efficacy of BACs and medicines. The article consists of description of different pleiotropic patterns established in experiments on the model of reactive oxygen species (ROS) generation by macrophages dependent on activity of specialized enzyme called Nox2-NAD(P)H oxidase (Nox2, EC 1.6.3.1). Moreover, it consists of explanation of pharmacodynamic nature of pleiotropic patterns by means of application Chou-Talalay median effect equalization and combination index (CI) theory. The novel theory explains unsolved until now universal aspects of activity BACs and medicines, such as slope angles of “dose-effect” dependences in the conditions relevant in vivo, and it is of fundamental interest. However, it has applications in experimental pharmacology, as it allows defining the choice of the individual compounds and combinations, modulating the trust effect selectively and efficiently. This knowledge opens up new approaches to medicines discovery and evaluation, their rational dosing and combining.