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updated Medications > Dopamine - clarity and structure
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GarrettS committed Jun 4, 2024
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Expand Up @@ -190,6 +190,7 @@ <h1>Parkinson's Disease Guide</h1>
<ul>
<li>GLYNAC</li>
<li>Creatine Monohydrate</li>
<li>Cacao</li>
<li class="neuroprotective anti-aggregant"><a href="#turmeric">Turmeric</a></li>
<li class="neuroprotective antifibrillogenic"><a href="#saffron">Saffron</a></li>
<li><a href="#coconut-oil">Coconut Oil</a></li>
Expand Down Expand Up @@ -639,21 +640,54 @@ <h3>Medications</h3>
<p>
Levodopa/Carbidopa are dopamine agonists. COMT inhibitors prevent the breakdown of dopamine. Both classes of drugs exhibit dopaminergic side effects.
</p>
<p>Dopamine agonists
<p>
Tolcapone, a COMT inhibitor, has been associated with a higher risk of liver damage, which can be severe in some cases.
</p>
<p>
Entacapone, another COMT inhibitor, has been linked to an increased risk of dyskinesias and other dopaminergic side effects.
</p>

<section>
<h4>Dopamine Replacement Therapy — Overview</h4>

<p>
Dopamine replacement therapy (DRT) for PD commonly includes levodopa/carbidopa (LD/DCC) and MAO-B inhibitors.
</p>
<p>
Replenishing dopamine levels in the brain helps alleviate motor symptoms such as tremors, rigidity, and bradykinesia (slowness, freezing), improving patients' quality of life. However, dopamine replacement therapy has other effects, good and bad.
</p>

<h4>Impact of Dopamine Agonists</h4>

<h5>Fibrillization</h5>
<p>
Dopamine agonists inhibit fibrillization by reacting with the α-synuclein. This is an advantage, as fibrils contribute to cellular damage, senescent cells, and neurodegeneration. However, it does so by an oxidative process that, in excess, also contributes to cellular damage and neurodegeneration.
</p>

<p>
Alpha-synuclein fibrillization inhibition must be balanced to both minimize and mitigate oxidative stress, and this requires a multi-faceted approach.
</p>

<h5>Neurochemical and Vitamin Imbalances</h5>
<p>
Dopamine agonists also deplete active vitamin B6 levels in the body. They do this by irreversibly binding to and permanently deactivating pyridoxal 5’-phosphate (P5P), the active form of vitamin B6. This leads to various side effects and exacerbates the progression of the disease, as B6 is essential for dopamine synthesis and is involved in other metabolic pathways.
</p>

<h5>Progressive Neurodegeneration</h5>
<p>
Dopamine is but one of many neurochemical systems in the midbrain. Focusing solely on the dopaminergic system without considering other neurotransmitter systems leads to inadequate symptom management, exacerbation of non-motor symptoms, and progressive neurodegeneration (PN).
</p>

<h4>Dopamine Replacement Therapy — Summary</h4>
<p>
Therefore, while dopamine replacement is beneficial, its use can be minimized to the least effective dose with a multi-faceted approach that addresses neuroprotection, neurorestoration, antioxidation, and mitochondrial health.
</p>
</section>

<section>
<h4>COMT Inhibitors</h4>
<p>
Tolcapone, a COMT inhibitor, has been associated with a higher risk of liver damage, which can be severe in some cases.
</p>
<p>
Entacapone, another COMT inhibitor, has been linked to an increased risk of dyskinesias and other dopaminergic side effects.
</p>
</section>

<h5>Dopaminergic Side Effects and PN</h5>
<p>
It's crucial to understand the interconnectedness of various neurochemical systems in the midbrain and their roles in PD management. Focusing solely on the dopaminergic system without considering other neurotransmitter systems can indeed lead to inadequate symptom management, exacerbation of non-motor symptoms, and progressive neurodegeneration (PN).
</p>
<p>
Dopamine agonists deplete active vitamin B6 levels in the body. They do this by irreversibly binding to and permanently deactivating pyridoxal 5’-phosphate (P5P), the active form of vitamin B6. This leads to various side effects and exacerbate the progression of the disease, as B6 is essential for dopamine synthesis and is involved in other metabolic pathways.
</p>

<section id="synuclean-d-and-minzasolmin">
<h4>SynuClean-D and Minzasolmin 🧪</h4>
Expand Down Expand Up @@ -877,6 +911,41 @@ <h4>GlyNAC</h4>
<section id="creatine">
<h4>Creatine Monohydrate</h4>
</section>

<section id="cacao">
<h4>Cacao</h4>
<!--
Antifibrillogenic and Anti-aggregant: Compounds in cacao may help prevent the formation and aggregation of α-synuclein fibrils, which are characteristic of PD pathology.
Neuroprotective and Antioxidant: Cacao's flavonoids possess antioxidant properties, potentially protecting neuronal structures from oxidative stress, which is implicated in PD progression.
Anti-inflammatory: Some components of cacao may have anti-inflammatory effects, which could help reduce neuroinflammation associated with PD.
Neurorestorative: By promoting mitochondrial health and possibly enhancing cellular processes like mitophagy, cacao might facilitate the recovery and regeneration of neural tissue in PD.
Dopaminergic side-effects: While cacao itself is not a direct treatment for PD symptoms, its potential neuroprotective and antioxidant properties could help mitigate some of the side effects associated with dopaminergic treatments used in PD management.
Sleep: Cacao contains compounds like theobromine, which may have stimulant effects, but individual responses to cacao consumption can vary regarding its impact on sleep. Moderate consumption may not significantly affect sleep patterns for most individuals.
Senolytic: While cacao has not been directly studied as a senolytic agent, its antioxidant and anti-inflammatory properties may indirectly contribute to cellular health and potentially impact senescent cells.
References:
"Cocoa procyanidins inhibit amyloid β-protein oligomerization and fibril formation" - published in the journal "Biochemistry" in 2012, investigated the inhibitory effects of cocoa procyanidins on the formation of amyloid fibrils, including those formed by α-synuclein. The researchers found cocoa procyanidins effectively inhibited fibril formation of amyloid β (Aβ) peptides, which are associated with Alzheimer's disease, and α-synuclein, suggesting a potential role in preventing protein aggregation in neurodegenerative diseases like Parkinson's
"Inhibition of α-synuclein fibrillization by dopamine analogs via reaction with the amino groups of α-synuclein and formation of dopamine adducts" - This study was published in the "Journal of Agricultural and Food Chemistry" in 2015, published in the "Journal of Agricultural and Food Chemistry" in 2015, evaluated the inhibitory effects of cocoa polyphenolic extract on the aggregation of α-synuclein. The researchers observed that cocoa polyphenols significantly inhibited the formation of α-synuclein aggregates and destabilized preformed fibrils, indicating a potential therapeutic strategy for Parkinson's disease and other synucleinopathies.
https://febs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1742-4658.2005.04792.x
Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405838/
Dietary Cocoa Flavanols Enhance Mitochondrial Function in Skeletal Muscle and Modify Whole-Body Metabolism in Healthy Mice
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538722/
-->
</section>
<section id="turmeric" class="neuroprotective antifibrillogenic">
<h4 data-safety-rating="9">
Turmeric
Expand Down Expand Up @@ -1515,7 +1584,7 @@ <h6>Melatonin References</h6>
</section>
<section id="quinones">
<h4>
Supplementation of Quinones (PQQ, CoQ10, Menaquinone (MK-4 and MK7 (k2)) for Mitochondrial Function
Mitochondrial Quinones (PQQ, CoQ10, Menaquinone (MK-4 and MK7 (k2))
</h4>
<p>
Quinones are a class of compounds that play a crucial role in maintaining mitochondrial function and overall cellular health.
Expand Down

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