Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Jan 2010
ReviewTargeting voltage-gated sodium channels for pain therapy.
Drugs inhibiting voltage-gated sodium channels have long been used as analgesics, beginning with the use of local anaesthetics for sensory blockade and then with the discovery that Nav-blocking anticonvulsants also have benefit for pain therapy. These drugs were discovered without knowledge of their molecular target, using traditional pharmacological methods, and their clinical utility is limited by relatively narrow therapeutic windows. ⋯ Together with recent advances in the technologies required to prosecute ion channels as drug targets, this has led to significant progress being made. This article reviews these developments and summarises current findings with these emerging new Nav inhibitors, highlighting some of the unanswered questions and the challenges that remain before they can be developed for clinical use.
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Expert Opin Investig Drugs · Nov 2009
ReviewAntivascular agents for non-small-cell lung cancer: current status and future directions.
Despite improvements in surgery and chemo(radio)therapy which have allowed for modest advances in the treatment of patients with non-small-cell lung cancer (NSCLC), survival remains poor and further improvements are needed. Attention over recent years has focused, therefore, on targeted therapies, with notable success in the development of antivascular drugs. ⋯ Bevacizumab, a humanized monoclonal antibody against the vascular endothelial growth factor (VEGF), when added to cytotoxic chemotherapy, was the first treatment to prolong the overall survival of patients with advanced NSCLC beyond 12 months, a significant breakthrough in the management of advanced NSCLC. Small-molecule tyrosine kinase inhibitors and alternative antivascular strategies such as VEGF-trap and vascular disrupting agents are also being investigated and have shown promise in clinical trials. This review summarizes the most recent and important findings in antivascular agents in NSCLC.
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The failure of drug candidates in clinical development remains a critical issue for the pharmaceutical and biotechnology industries. This article documents those oncology drugs discontinued in 2008 and briefly reviews reasons for termination of development. Source information was derived from a search of the Pharmaprojects database for drugs reaching phase I-III clinical trials.
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Expert Opin Investig Drugs · Oct 2009
ReviewFospropofol disodium, a water-soluble prodrug of the intravenous anesthetic propofol (2,6-diisopropylphenol).
Today, propofol or 2,6-diisopropylphenol is the anesthetic mainly used for monitored anesthetic care sedation and during intravenous anesthesia. The formulation, a lipid macroemulsion, shows several disadvantages. Therefore, during the past years considerable scientific effort has been undertaken to find either a better formulation or a prodrug of propofol. Fospropofol is the first propofol prodrug that has been intensively studied in man. It has been licensed in 2008 by the FDA for monitored anesthetic care sedation. ⋯ As the impact of an errorness drug assay for propofol liberated from fospropofol is not exactly defined, no clear conclusions can be drawn from the first published pharmacokinetic/pharmacodynamic studies. Fospropofol was well tolerated in the first two clinical studies and no serious side effects were reported. After characterization of the true pharmacokinetic/pharmacodynamics profile, fospropofol, an aqueous solution, has the potential to favorably compare with benzodiazepines for procedural sedation and also may be used for long-term sedation and intravenous anesthesia.
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Expert Opin Investig Drugs · Oct 2009
ReviewCurrent progress in the pharmacological therapy of fibromyalgia.
Fibromyalgia (FM) is a chronic musculoskeletal pain disorder often associated with fatigue, dyscognition, and sleep disturbances. Recent research advances highlight a critical role for aberrant central pain processing in FM, and, consistent with these data, the first three drugs approved by the FDA for FM over the past 2 years have a predominantly central mode of action. ⋯ The serotonin-norepinephrine reuptake inhibitors duloxetine and milnacipran have been approved more recently and are believed to reduce pain by increasing serotonin and norepinephrine concentrations in descending inhibitory pain pathways. Agents with multiple other mechanisms of action are in development and promise an assortment of therapeutic options for this complex disorder in the near future.