Current medicinal chemistry
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Bronchodilators, generally administered via metered dose or dry powder inhalers, are the mainstays of pharmacological treatment of stable COPD. Inhaled long-acting beta-agonists (LABA) and anticholinergics are the bronchodilators primarily used in the chronic treatment of COPD. Anticholinergics act as muscarinic acetylcholine receptor antagonists and are frequently preferred over beta-agonists for their minimal cardiac stimulatory effects and greater efficacy in most studies. ⋯ Some new LAMAs, including glycocpyrrolate, are suitable for once daily administration and, unlike tiotropium, have a rapid onset of action. New LAMAs and their combination with ultra-LABA and, possibly, inhaled corticosteroids, seem to open new perspectives in the management of COPD. Dual-pharmacology muscarinic antagonist-beta2 agonist (MABA) molecules present a novel approach to the treatment of COPD by combining muscarinic antagonism and beta2 agonism in a single molecule.
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Among 484 Hypericum L. (Guttiferae/Hypericaceae) species, widespread in warm temperate areas throughout the world, only H. perforatum is widely used in official medicine. Hypericum perforatum has been reported as an antidepressant, antiviral, antimicrobial, anti-inflammatory, and a healing agent. The main constituents of the Hypericum species are naphthodianthrones, primarily represented by hypericin and pseudohypericin, phloroglucinol derivatives, especially hyperforin, and flavonoids, such as quercetin, quercitrin, hyperoside and rutin. ⋯ However, only a few studies concerning the activity of extracts and isolated compounds were done in vivo. Also, data on the safe usage of Hypericum constituents as phytotherapeutics are scarce. Since some of Hypericum species are scarcely distributed or endemic as well as some of the secondary metabolites are presented in very small amounts, bio-production, especially endophytes, could represent an abundant and reliable source of pharmacologically active metabolites of Hypericum species for exploitation in pharmaceutical industry.
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Chronic obstructive pulmonary disease (COPD) is characterised by an abnormal inflammatory response of the lung to noxious particles or gases. The cellular inflammatory response in COPD is characterised by an increased number of inflammatory cells in the lungs. Although the molecular and cellular mechanisms responsible for the development of COPD are not well understood; several mediators are assumed to regulate the activation and recruitment of these inflammatory cells into the lung of COPD patients particularly those belonging to the chemokine family. ⋯ As such, every leading pharmaceutical company maintains a significant interest in developing agents that regulate leukocyte navigation as potential anti-inflammatory drugs. Drugs and antibodies targeting chemokines and their receptors are generally still in early stages of development and the results of clinical trial are awaited with great interest. These agents may not only provide improved management of COPD but also, importantly, indicate proof-of-concept to further clarify the role of chemokines in the pathophysiology of COPD.
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Oxygen (O(2)) is a vital element. Shortage of O(2) results in deranged metabolism and important changes in vascular tone with opposite effects on the systemic and pulmonary circulation. During hypoxemia, oxidative stress exposes the organism to a sort of accelerated senescence as well as to several acute untoward effects. ⋯ Consistent with this aim also is a careful scrutiny of instruments and procedures for monitoring the individual response to O(2) over time. Thus, at variance from classical pharmacological therapy, performing O(2) therapy requires a vast array of clinical and technical competences. The optimal integration of these competences is needed to optimize O(2) therapy on individual bases.
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RNA interference (RNAi) is an efficient process of posttranscriptional gene silencing. In recent years it has been developed into a new technology in biopharmaceutical fields of science. RNAi products include short interference RNA (siRNA) but also short hairpin RNA (shRNA), bifunctional short hairpin RNA (bi-shRNA) and microRNA (miRNA). ⋯ Among over 20 therapeutics that reached clinical trials, only few are still investigated. Another few are clinical candidates. The review focuses on RNAi products under clinical evaluation and their most promising new applications.