Current topics in medicinal chemistry
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Voltage-gated sodium channels are encoded by a family of ten structurally-related genes that are expressed in spatially and temporally distinct patterns, mainly in excitable tissues. They underlie electrical signalling in nerve and muscle. It has long been known that sodium channel blockers are anaesthetics as well as powerful analgesics when delivered at low concentrations. ⋯ There are indications that sodium channel blockers may also be useful in affective disorders and schizophrenia. The production of tissue-specific and eventually inducible knock out mice as well as genetic studies has proved useful in understanding the specialised role of individual types of sodium channels. The development of sub-type specific blockers has proved slower than anticipated, although the properties of naturally occurring toxin blockers suggest that subtype-specific blockers of sodium channels could be very useful clinically in the treatment of pain.
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Non-selective NSAIDs enhance the risk of serious ulcer complications (bleeding, perforation, obstruction), hospitalization and death about 3-10-fold. The gastrointestinal side effects of NSAIDs have a considerable economical burden, since they are responsible for 5-10 billion dollars in hospitalization charges and lost work time. NSAIDs cause gastrointestinal damage by both topical and systemic effects. ⋯ Current data suggest, that Coxibs are associated with a significantly lower risk of serious lower GI events than traditional NSAIDs. It is now under debate, who should receive COX-2-selective inhibitors instead of classical NSAIDs, since Coxibs are much more expensive. Data from cost-effectiveness studies suggest, that Coxibs should currently be used only in patients with high risks of GI complications.