This technology is a series of mitragynine analogs, altered for specific potency, efficacy and selectivity, for the treatment of pain and psychiatric disorders.
Unmet Need: Therapeutics addressing opioid-dependence and treatment-resistant psychiatric disorders
The dry leaf material of Mitragyna speciosa, or the Kratom plant, has a long history of medicinal use in humans. An increasing number of anecdotal reports have indicated its efficacy in treating diseases with very limited treatment options, including opioid dependence, treatment-resistant depression, anxiety, and pain. However, the clinical benefits of kratom are unclear due to the poor understanding of its biological and pharmacological effects.
The Technology: Synthesis of mitragynine analogs
This technology describes the synthesis of various analogs of mitragynine with defined pharmacological properties. The analogs possess substitutions that are key in tuning their potency, efficacy, and selectivity at opioid receptors. As such, the compounds described by this technology offer potential therapeutic leads for a number of psychiatric, pain, and substance abuse disorders.
Applications:
- Chronic pain treatments
- Treatments for depressive disorder, mood disorder, and anxiety disorder
- Treatments for substance use disorders
Advantages:
- Based off a natural plant-derivative with history of human use
- Variable potency, efficacy and selectivity at opioid receptors
- Potential for numerous clinical indications
Lead Inventor:
Dalibor Sames, Ph.D.
Patent Information:
Patent Pending (US20210179619)
Related Publications:
Bhowmik S, Galeta J, Havel V, Nelson M, Faouzi A, Bechand B, Ansonoff M, Fiala T, Hunkele A, Kruegel AC, Pintar JE, Majumdar S, Javitch JA, Sames D. “Site selective C-H functionalization of Mitragyna alkaloids reveals a molecular switch for tuning opioid receptor signaling efficacy.” Nat Commun. 2021 Jun 22;12(1):3858.
Chakraborty S, Uprety R, Slocum ST, Irie T, Le Rouzic V, Li X, Wilson LL, Scouller B, Alder AF, Kruegel AC, Ansonoff M, Varadi A, Eans SO, Hunkele A, Allaoa A, Kalra S, Xu J, Pan YX, Pintar J, Kivell BM, Pasternak GW, Cameron MD, McLaughlin JP, Sames D, Majumdar S. “Oxidative Metabolism as a Modulator of Kratom’s Biological Actions.” J Med Chem. 2021 Nov 25;64(22):16553-16572.
Chakraborty S, DiBerto JF, Faouzi A, Bernhard SM, Gutridge AM, Ramsey S, Zhou Y, Provasi D, Nuthikattu N, Jilakara R, Nelson MNF, Asher WB, Eans SO, Wilson LL, Chintala SM, Filizola M, van Rijn RM, Margolis EB, Roth BL, McLaughlin JP, Che T, Sames D, Javitch JA, Majumdar S. “A Novel Mitragynine Analog with Low-Efficacy Mu Opioid Receptor Agonism Displays Antinociception with Attenuated Adverse Effects.” J Med Chem. 2021 Sep 23;64(18):13873-13892.
Kruegel AC, Uprety R, Grinnell SG, Langreck C, Pekarskaya EA, Le Rouzic V, Ansonoff M, Gassaway MM, Pintar JE, Pasternak GW, Javitch JA, Majumdar S, Sames D. “7-Hydroxymitragynine is an active metabolite of mitragynine and a key mediator of its analgesic effects” ACS Central Science. 2019 May 29; 5(6): 992-1001.
Kruegel AC, Gassaway MM, Kapoor A, Váradi A, Majumdar S, Filizola M, Javitch JA, Sames D. “Synthetic and receptor signaling explorations of the Mitragyna alkaloids: mitragynine as an atypical molecular framework for opioid receptor modulators” J Am Chem Soc. 2016 May 18; 138(21): 6754-6764.
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