Acridine-iminodibenzyl chimeric compounds were previously introduced as a class of cholesterol-redistributing substances with antiprion effects. Here, we show that administration of the lead compound quinpramine to mice with experimental autoimmune encephalitis, an animal model of multiple sclerosis (MS), significantly ameliorates disease in preventive and therapeutic paradigms. Quinpramine treatment decreased the number of inflammatory CNS lesions, antigen-specific T-cell proliferation, and pro-inflammatory cytokines IFNgamma and IL-17. Quinpramine is thus an immunoregulatory drug that is a candidate pharmaceutical for MS.
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http://dx.doi.org/10.1016/j.expneurol.2008.10.001 | DOI Listing |
Curr Top Med Chem
November 2014
Department of Neuropathology, Heinrich Heine University of Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany.
An emerging common feature of the age-associated neurodegenerative disorders like Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD) is the ability of many disease-associated protein aggregates to induce conversion of a normal counterpart conformer leading to an acceleration of disease progression. Curative pharmacotherapy has not been achieved so far despite successes in elucidating pathomechanisms. Here, we review the pharmaceutical strategy of generating hybrid compounds, i.
View Article and Find Full Text PDFPLoS One
November 2011
Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Activation of inflammatory cells is central to the pathogenesis of autoimmune demyelinating diseases of the peripheral nervous system. The novel chimeric compound quinpramine--generated from imipramine and quinacrine--redistributes cholesterol rich membrane domains to intracellular compartments. We studied the immunological and clinical effects of quinpramine in myelin homogenate induced Lewis rat experimental autoimmune neuritis (EAN), a model system for acute human inflammatory neuropathies, such as the Guillain-Barré syndrome.
View Article and Find Full Text PDFDrug News Perspect
June 2010
Department of Neurology, Heinrich-Heine-University, Düsseldorf, Germany.
Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease of the central nervous system. Different therapeutic options are available, but all require parenteral application and some expose patients to potentially lethal adverse effects. The response to treatment remains variable and often incomplete.
View Article and Find Full Text PDFExp Neurol
June 2009
Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital, Gudrunstr. 56, D-44791 Bochum, Germany.
Exp Neurol
February 2009
Department of Neurology, University of Texas Southwestern, Dallas, USA.
Acridine-iminodibenzyl chimeric compounds were previously introduced as a class of cholesterol-redistributing substances with antiprion effects. Here, we show that administration of the lead compound quinpramine to mice with experimental autoimmune encephalitis, an animal model of multiple sclerosis (MS), significantly ameliorates disease in preventive and therapeutic paradigms. Quinpramine treatment decreased the number of inflammatory CNS lesions, antigen-specific T-cell proliferation, and pro-inflammatory cytokines IFNgamma and IL-17.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!