The selective nAChR, subtype agonist may therefore also be useful in the treatment of irritable bowel syndrome- constipation predominant.

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Technology Summary Opioid-induced constipation (OIC) is a major side-effect  especially with chronic use of opioids which limits the usefulness of these excellent pain relievers.  Constipation persists with chronic opioid use since tolerance does not occur to OIC. In contrast, tolerance is well known to occur for the analgesic effects of opioids. Therefore, it is desirable to reverse OIC that is accompanied by chronic opioid use. Conventional treatment strategies for constipation include use of laxatives, stool softeners and dietary fiber, but these are less than 50% effective in OIC cases and are associated with adverse side effects. Thus, identification of potential mechanisms that allow for the reversal or prevention of chronic OIC is greatly needed. Researchers at VCU have found that activation of a subset of nicotinic acetylcholine receptors (nAChR), which are abundantly present in the enteric nervous system, enhance gastrointestinal motility following chronic opioid use. Their studies show the activation of these specific nicotinic receptor subtypes by a partial agonist with high specific subtype affinity reverses OIC in vivo in mice with exposure to opioids. The specific  nAChR subtype is largely localized in the periphery and thus development of these peripherally active agonist will allow for the reversal of OIC but not affecting the function of nicotinic receptors in the brain. Persistent constipation due to chronic opioids occurs partly due to inflammation in the colon.  The selective nAChR, subtype agonist may therefore also be useful in the treatment of irritable bowel syndrome- constipation predominant. Benefits • Effective reversal of opioid induced constipation • Peripherally selective   • Useful in Irritable Bowel Syndrome-constipation predominant  Technology Status In vivo data available Patent Pending: US 62/294,455   US rights Available This technology is available for licensing to industry for further development and commercialization.  

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