title: Cell sensitivity, non-linearity and inverse effects.
abstract: It has been claimed that the homeopathic principle of 'similarity' (or 'similia') and the use of individualized remedies in extremely low doses conflicts with scientific laws, but this opinion can be disputed on the basis of recent scientific advances. Several mechanisms to explain the responsiveness of cells to ultra-low doses and the similarity as inversion of drug effects, have again been suggested in the framework of hormesis and modern paradoxical pharmacology. Low doses or high dilutions of a drug interact only with the enhanced sensitivities of regulatory systems, functioning as minute harmful stimuli to trigger specific compensatory healing reactions. Here we review hypotheses about homeopathic drug action at cellular and molecular levels, and present a new conceptual model of the principle of similarity based on allosteric drug action. While many common drugs act through orthostatic chemical interactions aimed at blocking undesired activities of enzymes or receptors, allosteric interactions are associated with dynamic conformational changes and functional transitions in target proteins, which enhance or inhibit specific cellular actions in normal or disease states. The concept of allostery and the way it controls physiological activities can be broadened to include diluted/dynamized compounds, and may constitute a working hypothesis for the study of molecular mechanisms underlying the inversion of drug effects.
authors: Department of Pathology and Diagnostics, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy. Electronic address: paolo.bellavite@univr.it.
authors: Paolo
authors: P
authors: Bellavite
authors: Medical Office, Via Molinara 14, 37135 Verona, Italy.
authors: Andrea
authors: A
authors: Signorini
authors: Department of Pathology and Diagnostics, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
authors: Marta
authors: M
authors: Marzotto
authors: Department of Pathology and Diagnostics, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
authors: Elisabetta
authors: E
authors: Moratti
authors: Department of Pathology and Diagnostics, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
authors: Clara
authors: C
authors: Bonafini
authors: Department of Pathology and Diagnostics, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
authors: Debora
authors: D
authors: Olioso
mesh_terms: D003585:Cell Biology; D004305:Dose-Response Relationship, Drug; D006705:Homeopathy / Q000379:methods*; D059165:Hormesis / Q000187:drug effects*; D006801:Humans; D008419:Materia Medica
chemical_list: D008419:Materia Medica
keywords: Allosteric regulation; Cell biology; Energy landscape; High-dilutions; Homeopathy; Hormesis; Pharmacodynamics; Receptors; Similia rule; Systems biology