Meet the Compound: SD-809 (dutetrabenazine)
Molecular Formula: C19H21D6NO
Molecular Weight: 324 g/mol
Mechanism of Action: Tetrabenazine reversibly inhibits monoamine re-uptake, which depletes monoamines and reduces involuntary movements.1 Auspex Pharmaceuticals, developer of SD-809, has shown that deuteration of tetrabenazine may slow its metabolism and decrease the need for large repeated doses.2,3
A Brief History of Deuterated Pharmaceuticals
By: Meredith Achey, BM
Deuteration, the selective substitution of deuterium for hydrogen in compounds that have known biological effects, can slow metabolism of these compounds by decreasing the rate of chemical reactions required to break down the compound, an effect known as the deuterium isotope effect.4 Deuteration has been explored since the 1960s as a way to potentially decrease toxicity of drug metabolites and extend biological half-life.2,4-8 As evidenced by the failure of several deuterated compounds prepared to date, deuteration can result in unexpected metabolic changes that render some deuterated compounds more toxic or less effective than their non-deuterated analogs (Table 1). However, several pharmaceutical firms have recently begun trials with promising new deuterated formulations, including Auspex Pharmaceuticals’ deuterated analog of tetrabenazine (SD-809) for use in individuals with HD and other hyperkinetic movement disorders. Preliminarily, SD-809 shows similar efficacy to tetrabenazine at lower doses and with a longer duration of action.3 Clinical trials of SD-809 in HD are currently underway.9, 10
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9 First time use of SD-809 in Huntington disease (First-HD).ClinicalTrials.gov. http://clinicaltrials.gov/ct2/show/NCT01795859. Accessed Dec. 2, 2013.
10 Long term safety study of SD-809 in patients chorea associated with Huntington disease (ARC-HD). ClinicalTrials.gov. http://clinicaltrials.gov/ct2/show/NCT01897896. Accessed Dec. 2,2013.
11 Elison C, Rapoport H, Laursen R, Elliott HW. Effect of deuteration of N-CH3 group on potency and enzymatic Ndemethylation of morphine. Science. 1961 Oct 13; 134(3485):1078-9.
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