Deepak Behera
Publication Details
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Antinociceptive sodium channel inhibitors having extended duration of action
The Journal of Pain. 2011; (4): 55
Existing treatment options for pain, such as the opioids, are not always effective and suffer from a wide range of side effects including potential for addiction. Saxitoxin (STX) is a highly potent naturally occurring sodium channel inhibitor that has been successfully employed in human clinical trials on >100 subjects for pain and certain neurological disorders. We hypothesized that our ability to prepare STX through de novo chemical synthesis would make possible the construction of modified forms of this compound having unique pharmacologic properties. Novel STXs were synthesized, characterized by patch clamp electrophysiology, and administered by local injection to the footpad of male Sprague Dawley rats. Antinociceptive efficacy and duration of action were measured through a variety of behavioral assays. Using this strategy, we have identified a STX derivative that provides up to six days of local analgesia in a rat nociception assay. We continue to evaluate the ADMET properties of our initial STX lead compounds through animal behavioral and radiological studies, and expect that such information will help guide the development of a STX-based therapeutic that offers improved efficacy and reduced side effects compared to existing treatment options for moderate to severe pain.
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