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Historical Review
Published in Gary M. Matoren, The Clinical Research Process in the Pharmaceutical Industry, 2020
Donald D. Vogt, Michael Montagne
On the other hand, there was evidence of a new approach. In 1931, James C. Munch published a classic study entitled Bioassays: A Handbook of Quantitative Pharmacology. This work demonstrated, among other things, that pharmaeometrics had become detached from classical pharmacology. Further, the book contained much data relating to drug evaluation. At the same time, no effort was devoted to the problem of reliability. In 1949, Leopold Ther published a booklet entitled Pharmacologische Methoden zur Auffindung von Arzneimitteln und Giften und Analyse ihrer Wirkungsweise. While such works were important, at this time problems were still being considered by the statistics of small numbers, up to the probability units. Later studies showed an increasing interest in statistical analysis of the biological evaluation of drugs that contributed to the control of the reliability of results.
Introduction
Published in Amritpal Singh Saroya, Reverse Pharmacology, 2018
Forward pharmacology is also called classical pharmacology. Pharmacognosy, the science dealing with study of physical, chemical and biological properties, cultivation and storage of herbal drugs is essentially viewed as classical pharmacology. The sciences of pharmacognosy and classical pharmacology are generally compared with reverse pharmacology (see definition).
Third Histamine Receptor: From Discovery to Clinics, Long-Lasting Love Story at INSERM and Bioprojet
Published in Divya Vohora, The Third Histamine Receptor, 2008
From the beautiful work performed a few years earlier by Jim Black, Robin Ganellin, and their colleagues, we had in hands the necessary tools to answer this question, that is, a series of compounds acting more or less selectively at either the H1 receptor (H1R) or the H2R, each of them being characterized by its apparent affinity constant. From their dose—response curves, we derived apparent dissociation constants of antagonists (using the Schild plot analysis) and the relative potencies of agonists. Using these classical pharmacology tools carefully, it became clear that we were dealing with a non-H1R, non-H2R: for instance, the effect of histamine was hardly affected by mepyramine at micromolar concentrations (whereas the drug displays nanomolar affinity at the H1R) and impromidine, a potent H2R agonist, behaved as a rather potent antagonist in our model, two examples among many others that fortified our conviction that we had discovered a novel histamine receptor.
Tetravalent biepitopic targeting enables intrinsic antibody agonism of tumor necrosis factor receptor superfamily members
Published in mAbs, 2019
Yanli Yang, Sherry H. Yeh, Shravan Madireddi, Wadim L. Matochko, Chen Gu, Patricia Pacheco Sanchez, Mark Ultsch, Gladys De Leon Boenig, Seth F. Harris, Brandon Leonard, Suzie J. Scales, Jing W. Zhu, Erin Christensen, Julie Q. Hang, Randall J. Brezski, Scot Marsters, Avi Ashkenazi, Siddharth Sukumaran, Henry Chiu, Rafael Cubas, Jeong M. Kim, Greg A. Lazar
Monoclonal antibodies are used as receptor agonists for research and therapeutic applications generally to mimic the cell signaling properties of a natural ligand.25 As drugs, antibodies can have advantages over natural ligands, including high production, good stability, favorable PK properties, and extensive manufacturing and clinical development experience.26 In contrast to conventional receptor–ligand antagonism, which plays to the strength of antibodies and generally follows more classical pharmacology, agonism can require more complex mechanistic elements depending on the nature of the receptor biochemistry. For some receptors, activation is promoted by ligand-induced dimerization, a mechanism that in principle can be readily mimicked by a bivalent IgG. In contrast, some receptors require higher-order crosslinking to signal, such as when cognate ligands are multimeric or where clustering of ligand-receptor complexes is driven by cell–cell interactions, as occurs for example within the immune synapse at the interface between T cells and antigen-presenting cells. Members of the TNFRSF are perhaps the most widely studied of this mechanistic class and are common antibody targets for drug development owing to their important roles in regulating cellular activation and proliferation.
Future prospects of accelerating neuroactive drug discovery with high-throughput behavioral phenotyping
Published in Expert Opinion on Drug Discovery, 2022
Since in most cases we do not know molecular targets or do not fully understand the molecular crosstalk underlying psycho-somatic illnesses, the effective solution for drug discovery can be the phenotypic screening, often referred to as classical pharmacology [1–3]. It is a viable and time-tested approach that is often greatly under-appreciated in the modern era of target-specific drug development. In fact, contrary to common opinion, a priori knowledge of the molecular targets is not a necessary pre-requisite for successful discovery or any regulatory approvals of drugs. This is clearly demonstrated by clinical practice and successful use of many existing legacy neuroceuticals [1–3].
Latest models for the discovery and development of rheumatoid arthritis drugs
Published in Expert Opinion on Drug Discovery, 2022
Bartosz Szostak, Anna Gorący, Bartłomiej Pala, Jakub Rosik, Łukasz Ustianowski, Andrzej Pawlik
The search for innovative treatment options has not been limited to classical pharmacology. Gang et al. [145] proposed the employment of thermochemotherapy in the management of RA. The combination of MTX and transforming growth factor β1 (TGF-β1) loaded into the nano-Fe3O4 composite chitosan-polyolefin formed a multifunctional drug-loaded hydrogel allowing the drug to be released gradually. This future potential therapy may have a powerful influence by simultaneously suppressing inflammation and cartilage regeneration. It has certainly opened a field for further research on modern RA therapies.