Sci Adv: What's new! The metabolic defects of the Parkinson's disease drug L-Doba are directly related to severe side effects in the patient's body!

January 11, 2021 // -- So far, researchers don't know why the drug levodopa (L-Dopa), which can reduce motor symptoms in people with Parkinson's disease, is declining after several years of use; One of the most common side effects is that patients exercise unconsciously; in a recent study published in the international journal Science Advances, scientists from institutions such as Uppsala University found that such problems were directly related to metabolic defects in the brain drug lyso-doba. Professor Per Andren, a researcher at
, said the findings could help develop new treatments for the developed Parkinson's disease, a slow death of nerve cells that produce the key neurotransmitter dopamine, which can lead to typical symptoms of the disease, such as stiffness and tremors in the body, and that treatments with the drug L-Doba (dopamine's precursor) are initially more effective, but after a few years, the dose effect becomes more short-lived.
patients also experience adverse side effects, such as the body's rapid alternating stiffness and uncontrolled movements, which become more severe over time.
In the end, the therapeutic benefits of L-Doba are clearly affected, and patients' symptoms become weaker, and researchers do not yet know which neurochemical mechanisms cause these side effects, an involuntary movement collectively known as L-Dopa-induced dyskinesia.
Photo Source: Pixabay/CC0 Public Domain uses a new technique called "substrate-assisted laser desorption/ionization mass spectrometry" (MALDI-MSI) that allows researchers to map a variety of neurotransmitters and other biological molecules directly into the brain tissues of non-human primates, which were previously almost impossible, with samples from a French bioscopic library.
This allowed the researchers to compare the brain tissue of two groups of Parkinson's disease animals in detail and clarify the differences between them; one group suffered from exercise complications from long-term L-Doba therapy; and the other group of individuals with the same degree of Parkinson's disease symptoms received the same L-Doba therapy, but the drug did not cause motor side effects in their bodies.
in a team with motor impairments, researchers detected abnormal levels of 3-O-methyl doba, a special metabolite when left-handed doba When converted to dopamine, 3-O-methyl dobba is formed, which is observed in all the brain regions examined, but to the researchers' surprise, a special brain region called the syroid is thought to be associated with movement disorders induced by lyso-doba. the
-related findings suggest that, in addition to previously identified brain mechanisms, other existing brain mechanisms may be the basis for inducing movement disorders in the body, which may not stem from the symposomes of the brain, but are most likely the effects of left-handed dopamine in other areas of the brain, or even a combination of the two.
Final Researcher Andren said that although there is a direct link between zodoba and complications of motor disorders in the body, we still do not have a specific molecular mechanism involved in the body's involuntary movement, which will require further research at a later stage.
other hand, this paper reveals the direct role of zotrol doba in the occurrence of movement disorders in the body (not related to dopamine).
may indicate that lyso-doba is likely to act alone on the body's brain.
() Original source: Elva Fridjonsdottir, Reza Shariatgorji, Anna Nilsson, et al. Mass spectrometry imaging identifies abnormally elevated brain l-DOPA levels and extrastriatal monoaminergic dysregulation in l-DOPA–induced dyskinesia, Science Advances (2021). DOI: 10.1126/sciadv.abe5948