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I am aware that dopamine cannot cross the blood-brain barrier, but can't it be pumped inside the cerebrospinal fluid via some permanent tube implant? Wouldn't Parkinson patients chose that over succumbing to the disease? Why hasn't it even been ever tried?

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Levo-Dopa is used as a first-line treatment of Parkinson's disease. Unlike dopamine, L-Dopa is able to cross the blood-brain barrier. There it is converted into dopamine. To prevent premature breakdown in the gastro-intestinal and circulatory system after oral intake, carbidopa can be co-administered. Also MAO-B inhibitors and COMT inhibitors can be applied to prevent breakdown of L-Dopa in the brain. Oral medication is preferable over invasive intracranial infusion of medication.

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Conversion of L-Dopa into dopamine. Source: ADHD treatments.

Dopamine agonists are also in use. Unlike L-Dopa, dopamine agonists are not converted into dopamine. Instead, they mimic dopamine effects in your brain. They aren't as effective as L-Dopa, but they last longer and may be used alongside L-Dopa to smooth the sometimes off-and-on effect.

Parkinson's disease is not fatal, but it can reduce longevity. The disease progresses more quickly in older patients, and may lead to severe incapacity within 10 - 20 years. Older patients also tend to have muscle freezing and greater declines in mental function and daily functioning than younger people. L-Dopa treatment in the long run causes adverse effects, such as dyskinesias, toxicity, or loss of efficacy (Marsden, 1994).

Reference
- Marsden, Clin Neuropharmacol (1994); 17: S2:S32-44

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  • $\begingroup$ so why do patients die in the end instead of living on "dopamine replacement" ? $\endgroup$ – ulak blade Jul 16 '15 at 5:49
  • $\begingroup$ @shortage_radeon - L-Dopa is a treatment, not a cure. Parkinson's is a progressive, degenerative and incurable disease, but not fatal. I amended the answer in response to your comment $\endgroup$ – AliceD Jul 16 '15 at 6:00
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    $\begingroup$ Quoting a faculty member at Moffitt Cancer Center: sometimes the goal now is to get patients dying with their particular disease, and not simply because of it using the treatments and therapies at medicine's disposal. Cures are remarkably elusive for complex diseases, where effective management strategies exist. $\endgroup$ – CKM Jul 16 '15 at 20:59
  • $\begingroup$ @AliceD I don't think this answers OP's question, which is why dopamine or an agonist cannot be pumped into the brain and thereby cure Parkinsons, or why that has never been tried. I do not know that answer, but I want to know it too. What's interesting is that it has been tried in 2 monkeys $\endgroup$ – Chelonian Aug 19 '15 at 5:21
  • $\begingroup$ @AliceD ...(you have to scroll through that to find the part on monkeys) at least once, and for one of them it rescued the motor deficit from an MPTP induced lesion for 9 days before problems with the method caused the pump to stop working. I was somehow both surprised and not surprised that this would work. I'd love to know whether anything more was ever followed up with this sort of approach. $\endgroup$ – Chelonian Aug 19 '15 at 5:22
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The blood-brain barrier isn't a bag that surrounds the brain that you could puncture and then inject dopamine. It is a thin layer of cells around every blood vessel and capillary in the brain that mediate transfer of substances between the blood and the brain cells. As such, it is incredibly complex and branched (as complex and branched as the myriad blood vessels in the brain).

In theory, you could inject dopamine directly into the cells of the brain, inside the barrier. But, the dopamine wouldn't diffuse far, and so wouldn't affect anything except for a very small area (millimeters?) around the injection point. So, to get an even distribution of dopamine, you'd need to inject at thousands (millions? more?) of points throughout the brain, and do it repeatedly.

And even with that, there's no guarantee that directly applying dopamine to the brain cells would actually help. In fact, bathing nerve cells in a neurotransmitter seems like a great way to mess up their signal transmission system.

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FDA recently approved the duodenal levodopa infusion pump. Idea is to wear the pump 18 hours a day, removing it at night. This allows for a small dose of levodopa to be injected through the day.

I can not yet add comments, only new post.

@shortage_radeon The leading causes of death, among patients with Parkinson's, were pneumonia and bronchitis. Swallowing becomes more difficult with time, leading to aspirated liquids into the lungs. While a feeding tube can assist, the most effective is working with a Speech Therapist on keeping those muscles active.

Thankfully exercise and diet have huge benefits for those of us with Parkinson's.

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