Metoclopramide-Induced Acute Dystonic Reactions May Be Associated With the CYP2D6 Poor Metabolizer Status and Pregnancy-Related Hormonal Changes

We report two cases of metoclopramide-induced acute dystonia in pregnant women and consider the role of genetic variation in the pathogenesis of the adverse effect. By whole-gene sequencing, we found that both women were CYP2D6 poor metabolizers. We theorize that CYP2D6 governs the risk of metoclopr...

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Main Authors: Eng Wee Chua (Author), Simon P. Harger (Author), Martin A. Kennedy (Author)
Format: Book
Published: Frontiers Media S.A., 2019-08-01T00:00:00Z.
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100 1 0 |a Eng Wee Chua  |e author 
700 1 0 |a Simon P. Harger  |e author 
700 1 0 |a Martin A. Kennedy  |e author 
245 0 0 |a Metoclopramide-Induced Acute Dystonic Reactions May Be Associated With the CYP2D6 Poor Metabolizer Status and Pregnancy-Related Hormonal Changes 
260 |b Frontiers Media S.A.,   |c 2019-08-01T00:00:00Z. 
500 |a 1663-9812 
500 |a 10.3389/fphar.2019.00931 
520 |a We report two cases of metoclopramide-induced acute dystonia in pregnant women and consider the role of genetic variation in the pathogenesis of the adverse effect. By whole-gene sequencing, we found that both women were CYP2D6 poor metabolizers. We theorize that CYP2D6 governs the risk of metoclopramide-related acute dystonia through its role in the synthesis of serotonin, which inhibits the dopamine tone. The effect of CYP2D6 poor metabolism is exaggerated by rises in the estrogen levels during pregnancy, as the hormone augments dopamine sensitivity. Together, the two factors may create a hyper-dopaminergic state that is easily upset by metoclopramide, resulting in acute dystonia. 
546 |a EN 
690 |a metoclopramide 
690 |a acute dystonia 
690 |a CYP2D6 
690 |a poor metabolizer 
690 |a pregnancy 
690 |a estrogen 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
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786 0 |n Frontiers in Pharmacology, Vol 10 (2019) 
787 0 |n https://www.frontiersin.org/article/10.3389/fphar.2019.00931/full 
787 0 |n https://doaj.org/toc/1663-9812 
856 4 1 |u https://doaj.org/article/cd28b3597e4d487db75a6033c0a06924  |z Connect to this object online.