Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2015
Evaluation of sodium nitroprusside for controlled hypotension in children during surgery.
(1) To define the onset and offset of the blood-pressure-lowering effects of sodium nitroprusside (SNP) for use in developing instructions for dose titration in children undergoing a surgical or medical procedure, and (2) to assess the safety of SNP administration in pediatric patients requiring controlled reduction of blood pressure. ⋯ We determined that 0.3 μg/kg/m is a reasonable starting dose for SNP in pediatric patients requiring controlled hypotension. The infusion rate can then be increased to achieve the desired reduction in blood pressure. On the basis of our results, we found an average infusion rate of 1 μg/kg/min might be appropriate. Of note, no cyanide toxicity was reported, and no measureable cyanide levels were detected in any blood samples obtained during the study. http://clinicaltrials.gov/show/NCT00135668.
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Frontiers in pharmacology · Jan 2015
Inhibition of voltage-gated sodium channels by sumatriptan bioisosteres.
Voltage-gated sodium channels are known to play a pivotal role in perception and transmission of pain sensations. Gain-of-function mutations in the genes encoding the peripheral neuronal sodium channels, hNav1.7-1.9, cause human painful diseases. Thus while treatment of chronic pain remains an unmet clinical need, sodium channel blockers are considered as promising druggable targets. ⋯ Accordingly, we show that (S)-22b likely binds the conserved local anesthetic receptor within voltage-gated sodium channels. Combining these results with the previous ones, we hypothesize that use-dependent sodium channel blockade contributes to the analgesic activity of (R)-31b and (S)-22b. These later compounds represent promising lead compounds for the development of efficient analgesics, the mechanism of action of which may include a dual action on sodium channels and 5HT1D receptors.
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Frontiers in pharmacology · Jan 2015
ReviewA Review of Swertia chirayita (Gentianaceae) as a Traditional Medicinal Plant.
Swertia chirayita (Gentianaceae), a popular medicinal herb indigenous to the temperate Himalayas is used in traditional medicine to treat numerous ailments such as liver disorders, malaria, and diabetes and are reported to have a wide spectrum of pharmacological properties. Its medicinal usage is well-documented in Indian pharmaceutical codex, the British, and the American pharmacopeias and in different traditional medicine such as the Ayurveda, Unani, Siddha, and other conventional medical systems. This ethnomedicinal herb is known mostly for its bitter taste caused by the presence of different bioactive compounds that are directly associated with human health welfare. ⋯ In this regard, plant biotechnological applications such as micropropagation, synthetic seed production, and hairy root technology can play a significant role in a holistic conservation strategy. In addition to micropropagation, storage of these valuable genetic resources is equally important for germplasm preservation. However, more advanced research is warranted to determine the activities of bioactive compounds in vitro and in vivo, establish their underlying mechanisms of action and commence the process of clinical research.
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Frontiers in pharmacology · Jan 2014
ReviewImplementation of pharmacokinetic and pharmacodynamic strategies in early research phases of drug discovery and development at Novartis Institute of Biomedical Research.
Characterizing the relationship between the pharmacokinetics (PK, concentration vs. time) and pharmacodynamics (PD, effect vs. time) is an important tool in the discovery and development of new drugs in the pharmaceutical industry. The purpose of this publication is to serve as a guide for drug discovery scientists toward optimal design and conduct of PK/PD studies in the research phase. This review is a result of the collaborative efforts of DMPK scientists from various Metabolism and Pharmacokinetic (MAP) departments of the global organization Novartis Institute of Biomedical Research (NIBR). ⋯ This review focuses on three important elements of successful PK/PD studies, namely partnership among key scientists involved in the study execution; parameters that influence study designs; and data analysis and interpretation. Specific examples and case studies are highlighted to help demonstrate key points for consideration. The intent is to provide a broad PK/PD foundation for colleagues in the pharmaceutical industry and serve as a tool to promote appropriate discussions on early research project teams with key scientists involved in PK/PD studies.