How Levodopa Works Affected by Certain Parkinson’s Drugs, Study Finds

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The use of several Parkinson’s disease drugs was significantly associated with the increased abundance of a bacterial enzyme that converts levodopa to dopamine in the gut, potentially reducing the availability of levodopa in the brain, according to one study.

In patients with rapidly progressive Parkinson’s disease, the approved treatment Comtan (entacapone) increased enzyme abundance, suggesting that this drug may reduce the impact of levodopa.

These findings support further research into the effect of Parkinson’s disease drugs on gut microbial changes, the researchers noted.

The Dutch study, “Bacterial Intestinal Tyrosine Decarboxylase Associates with Clinical Variables in a Longitudinal Cohort Study in Parkinson’s DiseaseWas published in the journal NPJ Parkinson’s Disease.

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Parkinson’s disease is marked by the loss of dopaminergic neurons in the brain, nerve cells that communicate with other neurons by releasing the signaling molecule known as dopamine.

A lack of dopamine leads to characteristic motor symptoms. Yet patients may also experience non-motor symptoms such as cognitive impairment, depression, sleep disturbances, and more problems with the gastrointestinal (GI) tract.

One of the main treatments used to treat symptoms of Parkinson’s disease is levodopa, a precursor to dopamine. The drug is taken up by dopaminergic neurons, which convert it into dopamine.

Studies suggest that some bacteria in the gut produce an enzyme called tyrosine decarboxylase (TDC), which can convert levodopa to dopamine. This reaction can restrict the availability of levodopa in the bloodstream and possibly in the brain, reducing its effectiveness.

Researchers based at the University of Groningen in the Netherlands questioned whether increased exposure to other drugs used to treat Parkinson’s disease affects the abundance of bacterial CDD, which may ultimately impact the disease. effectiveness of levodopa.

To find out, the team measured the abundance of the bacterial gene that codes for TDC – tdc – in stool samples taken from 67 patients with Parkinson’s disease and 65 healthy control subjects for two years. Patients and controls were matched on gender, age, body mass index (body fat content), and antibiotic use in the previous month.

In patients, the duration of motor and non-motor symptoms at baseline (baseline) was approximately eight years. From baseline to follow-up, there was a significant increase in the mean equivalent daily dose of levodopa (LEDD) – the total contribution made by each drug against Parkinson’s disease.

During the study, there was a significant worsening in patients with Parkinson’s disease in intellectual function, mood and activities of daily living, but a significant improvement in motor function, which “can be explained by the significant increase in LEDD over time,” the team wrote. .

At the beginning, tdc was very common in patients with Parkinson’s disease (98%) and controls (97%). Likewise, similar results were observed during follow-up (98% vs. 100%). At this time, people with Parkinson’s disease tended to have a greater abundance of tdc that controls.

However, the increase in tdc abundance over time was significantly higher in patients compared to controls, with an average increase of 2.6 times.

“The results indicate that over time, tdc-the abundance of genes increases more rapidly in [Parkinson’s disease] patients compared to [healthy control] subjects, ”the researchers wrote.

“Here, we did not find a significant correlation between the dosage of levodopa and tdc-the abundance of genes, ”they added. “This discrepancy could be explained by the relatively low proportion of high doses of levodopa in this study.”

The patients’ gastrointestinal symptoms were more severe than those of the controls both at baseline and at follow-up. Over time, only Wexner’s constipation scores increased significantly, but not the Rome III scores for constipation and defecation combined.

Although LEDD increased over time, there was no significant increase in individual drug use in patients, “possibly due to changes in the type of drug,” wrote investigators. When evaluating the treatments shared by the two groups, patients initially used significantly more anticholinergic drugs, which are prescribed to relieve motor symptoms.

The team then looked at how different Parkinson’s therapies affected tdc levels over time. Dose changes of Comtan, Requip (ropinrole) and Mirapex (pramipexole) have been associated with increases in tdc abundance, while Azilect (rasagiline) contributed to a reduction in tdc quantity over time.

Wexner’s total constipation scores were significantly associated with less tdc abundance. After correcting for Wexner scores, the difference in exposure to treatments for Parkinson’s disease still contributed to the tdc abundance results except for Requip.

“The results indicate that prolonged exposure to these anti-[Parkinson’s disease] drugs, with the exception of levodopa, have contributed to tdc-the abundance of genes regardless of changes in gastrointestinal symptoms as measured by Wexner scores, ”the scientists noted.

Since patients with Parkinson’s disease change their therapeutic doses as the disease progresses, the team compared the impact of tdc abundance of those who progressed slowly versus those who progressed quickly. Exposure to levodopa and Comtan significantly increased, while use of Mirapex significantly decreased in the rapid group compared to the slow progression group.

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In the slow growing group, Requip has now largely contributed to tdc levels, but not Comtan. This meaning was no longer found when correcting Wexner scores.

In the rapid group, however, only the use of Comtan significantly contributed to the change in tdc abundance.

“In summary, these observations indicate that the change in exposure to anti-[Parkinson’s disease] drugs, like [Comtan], may be an important factor contributing to an increase in tdc-abundance of rapidly growing genes [Parkinson’s disease] patients, ”the researchers explained. At the same time, “other anti-[Parkinson’s disease] drugs help tdc-abundance of slowly growing genes [Parkinson’s disease] the patients.”

“The present study involves important associations between anti-[Parkinson’s disease] drugs and intestinal bacteria tdc-the abundance of genes, ”wrote the authors. “These associations point to complex interactions between anti-[Parkinson’s disease] medications, gastrointestinal symptoms and gut bacteria tdc-the abundance of genes, which justifies further research.


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