[Ronhutton]

Thinking of novel ways to get dopamine (not levodopa) into the brain, it can;t be done orally (doesn't pass the BBB, so a patch is no good either). We have mentioned the nasal route of drug delivery to the brain before. It bypasses the BBB. This route is used increasingly for many illnesses.

Dopamine can be stored in the brain,
http://encyclopedia2.thefreedictiona...+hydrochloride
Dopamine is manufactured inside dopamine neurons in a controlled manner from the amino acid precursor L -tyrosine, which mammals obtain through the normal diet. Dopamine is then stored in vesicles within the nerve terminals

Dopamine is fairly soluble in water, (60 grms/100mls), so what if we made an aqueous solution and delivered an aerosol spray through the nose?
Would we only need a quick spray hourly if it can be stored. I have read we make most dopamine during the night and store it. The supply gets thin by evening which is presumably why I flag evenings.
One thing we would have to take care of is dopamine can do lots of other things in the body, such as heart rate,

http://www.tiscali.co.uk/lifestyle/h...100000840.html
At lower doses it binds to dopamine receptors in the kidney, gut, brain and heart causing the blood vessels in these organs to widen. This improves the blood flow and therefore improves the amount of oxygen supplied to the organs. It also causes an increase in urine output from the kidneys. When the dose of dopamine is increased, beta-receptors, which are found on the heart muscle, are also activated. This causes an increase in the rate and strength at which the heart beats

However these effects are in the body, and we are putting it into the brain where it is locked in since it can't cross the BBB into the body.
I can't believe it could be that simple but what do the other tame chemists think? It should be easy to obtain from a lab chemical supplier, it is not on prescription.
Ron

[reverett123]

Some random thoughts-

Rather than dopamine, why not stick with sinemet since it is readily available? If the carboxylaise (?) is a problem, is an aqueous solution necessarily better than, say, an alcohol one in terms of solubility of the two components and the penetration and dispersal into the target?

You mentioned storage of dopamine- another approach might be a way of enhancing its release rather than adding to the total.

[olsen]

Does not Glutathione enhance the release of dopamine? madelyn

[Ronhutton]

Rick,
You could not use sinemet in the nasal route, you would get carbidopa into the brain as well as levodopa. The carbidopa would prevent the conversion to dopamine even of any small natural levodopa in the nrain. I imagine you would be totally imobile, incapable of making dopamine in the brain. Carbidopa can't pass the BBB so when taken orally in sinemet, the levodopa passes into the brain but not the carbidopa. I think you would need to use pure dopamine. You could use levodopa, but as I understand it, we have an impaired ability to convert it to dopamine.

Madelyn,
Yes glutathione is claimed to enhance dopamine formation,but I am not sure what you are suggesting. I am looking for ways to get pure dopamine into the brain. Enhancing natural production is a different topic, or have I misunderstood?
Ron

[reverett123]

Either that or I'm wrong and will look silly for the first time in my life.

Why not take advantage of the fact that so many things make the BBB fail the PWP and engineer a temporary BBB "failure" to coincide with a peak in the curve of L-dopa or mucuna or whatever that you are trying to deliver into the brain?

Example: Assume that sugar makes it permeable for an hour. And assume that mucuna triggers an increase in dopamine production. Fiddle with the timing to get the two Tmax events to coincide.

Too much trial and error for a few white rats but it is worth thinking about.

[Ronhutton]

Hi Rick,
I think we are going off at tangents, discussing everything but the original suggestion. Why not if we can store dopamine, get it into the brain easily, by the nasal route???? It is fast and avoids side effects.
I shouldn't like to spend time trying to coincide a malfunction in the BBB with trying to rush past a blob of levodopa!! That is even if sugar opens the BBB, and if it did, toxins can also rush in. We need ways of tightening the BBB.
In any case, levodopa easily passes the BBB anyway, so why attempt to do it the hardest way possible. Just keep taking your sinemet.
Also, you are going back to oral delivery, with all its side effect problems.
These suggestons are a different thread, why not debate the pros and cons of this idea.
Ron

[reverett123]

Are you familiar with Wm Frey?
http://www.ncbi.nlm.nih.gov/sites/en...+h.+frey+brain

He has about 15 publications that look interesting.

[Ronhutton]

Hi Rick,
Well at least we are back on track LOL
Yes I know him well. We corresponded on the nasal route at length 5 years ago. He is an expert on this route. I have a lever arch file on the nasal delivery of drugs. Back to the topic, I must find a source of pure dopamine next.
Ron

[olsen]

Hello Ron, my post was in response to rick's comment:
"You mentioned storage of dopamine- another approach might be a way of enhancing its release rather than adding to the total. "
I remembered that glutathione enhanced release of dopamine, thus the potential problem of using IV glutathione being depletion of dopamine stores that are already woefully depleted.
madelyn

madelyn

[Ronhutton]

It has been done before!! They even used dopamine.
It got to the brain via the nasal passage,
"These molecules appeared rapidly in the CSF, although hard evidence of direct transfer
from the nose remains elusive."

So they had problems using scientific tests to get hard evidence of how much reached the target.
But PDers can test easily by measuring effect on our symptoms. The effect would be extremely rapid, with no dyskinesia or side effects, since none goes into the blood.

However, they recognise the value of the nasal route.
"The nasal administration of drugs offers advantages over administration by intravenous
injection. Drugs can be rapidly absorbed through the nasal mucosa, resulting in a rapid onset
of action, and also avoiding degradation in the gastrointestinal tract and first-pass metabolism
in the liver. Targeting the brain via nasal administration offers potential for the development
of new drugs."
See
http://www.diva-portal.org/diva/getD...__fulltext.pdf

Ron