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Old Drugs (old + drug)
Selected AbstractsAnti-tumor mechanisms of valproate: A novel role for an old drugMEDICINAL RESEARCH REVIEWS, Issue 5 2002Roman A. Blaheta Abstract Valproic acid (VPA, 2-propylpentanoic acid) is an established drug in the long-term therapy of epilepsy. During the past years, it has become evident that VPA is also associated with anti-cancer activity. VPA not only suppresses tumor growth and metastasis, but also induces tumor differentiation in vitro and in vivo. Several modes of action might be relevant for the biological activity of VPA: (1) VPA increases the DNA binding of activating protein-1 (AP-1) transcription factor, and the expression of genes regulated by the extracellular-regulated kinase (ERK)-AP-1 pathway; (2) VPA downregulates protein kinase C (PKC) activity; (3) VPA inhibits glycogen synthase kinase-3, (GSK-3,), a negative regulator of the Wnt signaling pathway; (4) VPA activates the peroxisome proliferator-activated receptors PPAR, and ,; (5) VPA blocks HDAC (histone deacetylase), causing hyperacetylation. The findings elucidate an important role of VPA for cancer therapy. VPA might also be useful as low toxicity agent given over long time periods for chemoprevention and/or for control of residual minimal disease. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 5, 492,511, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10017 [source] 4-aminopyridine: New life for an old drugANNALS OF NEUROLOGY, Issue 1 2010Stephen L. Hauser MD Editor No abstract is available for this article. [source] Statins and osteoporosis: new role for old drugsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2006Satyawan B. Jadhav Osteoporosis is the most common bone disease, affecting millions of people worldwide and leading to significant morbidity and high expenditure. Most of the current therapies available for its treatment are limited to the prevention or slowing down of bone loss rather than enhancing bone formation. Recent discovery of statins (HMG-CoA reductase inhibitors) as bone anabolic agents has spurred a great deal of interest among both basic and clinical bone researchers. In-vitro and some animal studies suggest that statins increase the bone mass by enhancing bone morphogenetic protein-2 (BMP-2)-mediated osteoblast expression. Although a limited number of case,control studies suggest that statins may have the potential to reduce the risk of fractures by increasing bone formation, other studies have failed to show a benefit in fracture reduction. Randomized, controlled clinical trials are needed to resolve this conflict. One possible reason for the discrepancy in the results of preclinical, as well as clinical, studies is the liver-specific nature of statins. Considering their high liver specificity and low oral bioavailability, distribution of statins to the bone microenvironment in optimum concentration is questionable. To unravel their exact mechanism and confirm beneficial action on bone, statins should reach the bone microenvironment in optimum concentration. Dose optimization and use of novel controlled drug delivery systems may help in increasing the bioavailability and distribution of statins to the bone microenvironment. Discovery of bone-specific statins or their bone-targeted delivery offers great potential in the treatment of osteoporosis. In this review, we have summarized various preclinical and clinical studies of statins and their action on bone. We have also discussed the possible mechanism of action of statins on bone. Finally, the role of drug delivery systems in confirming and assessing the actual potential of statins as anti-osteoporotic agents is highlighted. [source] New concerns about old drugs: Valvular heart disease on ergot derivative dopamine agonists as an exemplary situation of pharmacovigilanceMOVEMENT DISORDERS, Issue 6 2004Olivier Rascol MD [source] Do Off-Label Drug Practices Argue Against FDA Efficacy Requirements?AMERICAN JOURNAL OF ECONOMICS AND SOCIOLOGY, Issue 5 2008A Critical Analysis of Physicians' Argumentation for Initial Efficacy Requirements The amended Food, Drug and Cosmetics Act requires efficacy certification for a drug's initial uses ("on-label"), but does not require certification before physicians may prescribe the drug for subsequent uses ("off-label"). Does it make sense to require FDA efficacy certification for new drugs but not for new uses of old drugs? Using a sequential online survey, we carried on a "virtual conversation" with some 500 physicians. The survey asked whether efficacy requirements should be imposed on off-label uses; almost all physicians said no. It asked whether the efficacy requirements for initial uses should be dropped, and most physicians said no. We then asked respondents whether opposing efficacy requirements in one case but not the other involved an inconsistency. In response, we received hundreds of written commentaries. We organize and discuss these commentaries with an eye to understanding how the medical market certifies off-label drug uses and how this compares to FDA certification. Does off-label medicine use suggest that efficacy requirements should be placed on new uses of old drugs? Does it suggest that efficacy requirements on new drugs should be lifted? We explore these questions, and ask whether the response of many of the doctors exhibits the familiar behavior bias toward the status quo. [source] |