HelixTalk Episode #82 - Let’s Get Heavy! Deuterium Substitution as a Pathway for Drug Design

Date posted: August 7, 2018, 6:00 am

In this episode, we take a closer look at deuteration, specifically involving the medication deutetrabenazine (discussed back in episode 76). We feature a guest contributor from our pharmacy sciences department who assists us as we look at the drug design aspects of this unique molecule and its implications for research moving forward.

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Key Concepts

1. Deuteration is not a new concept in medicine. It has been discussed for decades; however it was only recently (2017) that deutetrabenazine became the first such agent to receive FDA approval.
2. Deuteration improves stability of carbon bonds, thus changing drug metabolism and extending drug half life.
3. The process may also alter metabolic pathways. While it won’t lead to formation of a new metabolite, it may change the preferred product. Sometimes this is good and could decrease production of a toxic metabolite, but not always! Thus careful research is needed before bringing a drug to market.
4. There are a number of drugs in the pipelines which also undergo deuteration, including deuterated forms of dextromethorphan (in combination with quinidine) for dementia, paroxetine for hot flashes, pioglitazone for diabetes, and polyunsaturated fatty acids for Parkinson’s disease and dementia.

References

1. Frank S, et al. Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease. A Randomized Clinical Trial. JAMA. 2016; 316 (1): 40-50.
2. DeWitt SH and Maryanoff BE. Deuterated Drug Molecules: Focus on FDA-Approved Deutetrabenazine. Biochemistry. 2018; 57 (5): 472-3.