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The main aims of the study were to disclose the influence of the structure on the solubility, distribution and permeability of the parent substances, iproniazid (IPN), isoniazid (INZ) and isonicotinamide (iNCT), at 310.2 K and to evaluate how the presence of cyclodextrins (2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and methylated β-cyclodextrin (M-β-CD)) affects the distribution behavior and diffusion properties of a model pyridinecarboxamide derivative, iproniazid (IPN). The following order of decreasing the distribution and permeability coefficients was estimated: IPN > INZ > iNAM.
View Article and Find Full Text PDFMinimizing Polymorphic Risk through Cooperative Computational and Experimental Exploration.
J Am Chem Soc
September 2020
Department of Chemistry, Durham University, South Road, Durham DH1 3LE, U.K.
We combine state-of-the-art computational crystal structure prediction (CSP) techniques with a wide range of experimental crystallization methods to understand and explore crystal structure in pharmaceuticals and minimize the risk of unanticipated late-appearing polymorphs. Initially, we demonstrate the power of CSP to rationalize the difficulty in obtaining polymorphs of the well-known pharmaceutical isoniazid and show that CSP provides the structure of the recently obtained, but unsolved, Form III of this drug despite there being only a single resolved form for almost 70 years. More dramatically, our blind CSP study predicts a significant risk of polymorphism for the related iproniazid.
View Article and Find Full Text PDFParoxetine Administration Affects Microbiota and Bile Acid Levels in Mice.
Front Psychiatry
June 2020
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
Recent interest in the role of microbiota in health and disease has implicated gut microbiota dysbiosis in psychiatric disorders including major depressive disorder. Several antidepressant drugs that belong to the class of selective serotonin reuptake inhibitors have been found to display antimicrobial activities. In fact, one of the first antidepressants discovered serendipitously in the 1950s, the monoamine-oxidase inhibitor Iproniazid, was a drug used for the treatment of tuberculosis.
View Article and Find Full Text PDFAntidepressants, antimicrobials or both? Gut microbiota dysbiosis in depression and possible implications of the antimicrobial effects of antidepressant drugs for antidepressant effectiveness.
J Affect Disord
January 2017
Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
Objectives: The first drug repurposed for the treatment of depression was the tuberculostatic iproniazid. At present, drugs belonging to new classes of antidepressants still have antimicrobial effects. Dysbiosis of gut microbiota was implicated in the development or exacerbation of mental disorders, such as major depressive disorder (MDD).
View Article and Find Full Text PDFSerendipity and psychopharmacology.
J Psychosoc Nurs Ment Health Serv
October 2010
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
This article describes several examples where the development of drugs and devices for use in psychiatry followed from initial serendipitous observations. The potential psychotropic properties of chlorpromazine (Thorazine(®)) were first noted in surgical patients when the drug was being investigated as a potentiator of anesthesia. Similar findings were noted with iproniazid (Marsilid(®)), developed for the treatment of tuberculosis, and the drug was later released for clinical use as an antidepressant agent.
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