Safer Nonaddicting and Nonabusable Analgesics: Targeting Truncated 6-Transmembrane Exon 11 Variants of the Oprm 1 Gene for Battlefield Pain
Technical Report,15 Jun 2017,14 Jun 2018
Sloan Kettering Institute for Cancer Research New York United States
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The key positive findings of this grant are 7OH mitragynine 7OH is a potent opioid analgesic devoid of respiratory depression separating its analgesic actions from classical mu opioid modulators like morphine, oxycodone and fentanyl. 7OH has distinct central analgesic mechanism of action which is dependent on the adrenergic alpha2A receptors which in turn is dependent on 6TM-MOR-1 sites. Systemically, 7OH is less dependent on 6TMMOR-1 receptors and primarily acts through 7TM-MOR-1 sites just like morphine. The negative findings are 7OH retains addictive and abuse liability similar to morphine irrespective of its route of administration. Both central as well as systemic receptor mechanisms lead to addiction liability. More conclusive studies where 6TM mechanisms can be separated from 7TM MOR-1 mechanisms may lead to better understanding of the target labeled by 7OH.