Just a single dose via a nasal nebuliser and a spray bottle is used.
They say,

"In recent years, interest has been expressed in the use of the nasal route to deliver drugs to the brain for treatment of common neurological diseases such as Alzheimer's and Parkinson's, because delivering drugs to the olfactory bulb in the upper regions of the nasal cavity can bypass this barrier."

Why they haven't spent more time on using dopamine itself, I don't know.
Ron

http://www.in-pharmatechnologist.com...o-enter-trials
Nasal Alzheimer's drug to enter trials
08-Sep-2005
Related topics: Materials & Formulation, Drug delivery systems

A clinical trial will shortly get underway to see if insulin, delivered intranasally using an atomiser developed by Kurve Technology, can improve short-term memory in Alzheimer's disease patients.

Kurve is donating 10 of its ViaNase electronic atomiser devices to the clinical researchers, from Veterans Affairs Puget Sound Health Care System and the University of Washington in the US.

ViaNase takes the form of a nasal nebuliser and a spray bottle, and makes use of the electronic atomiser to produce finely-controlled particle dispersions. Studies have shown that the device delivers drug to the entire nasal mucosa, penetrating far deeper into the nasal cavity than traditional nasal drug delivery devices. Coverage of the nasal mucosa and depth of drug penetration are two important elements of effective and efficient liquid-based intranasal drug treatments.


The 21-day trial will study the effect of intranasal insulin delivery on the short-term memory of 30 patients with early stage Alzheimer's disease. Previous studies conducted at the VA and the University of Washington have demonstrated that a single dose of intranasal insulin improved memory function for some patients with Alzheimer's.




Suzanne Craft, the principle investigator in the trial, said that the team had been searching for a device that efficiently delivers insulin via the nasal route. "The fact that ViaNase allows patients to self-administer study formulations at home is crucial to this study," she commented.


The blood-brain barrier that separates the brain interstitial fluid from the circulating blood provides an efficient barrier for the diffusion of most drugs from the blood to the brain and central nervous system (CNS). In recent years, interest has been expressed in the use of the nasal route to deliver drugs to the brain for treatment of common neurological diseases such as Alzheimer's and Parkinson's, because delivering drugs to the olfactory bulb in the upper regions of the nasal cavity can bypass this barrier.


According to the Alzheimer's Association, an estimated 4.5 million people have Alzheimer's disease in the US, a number expected to increase to 11-16 million by 2050. Finding a treatment that could delay onset by five years could reduce the number of individuals with Alzheimer's disease by nearly 50 percent after 50 years.

At least patient power is forcing them to upturn a few more stones!
Ron

http://www.depressedmetabolism.com/n...-to-the-brain/
The implications of direct nose-to-brain transport went largely unnoticed until the 1990s, when enhanced public attention to brain research compelled scientists to discover and implement effective treatment strategies in an effort to combat the upsurge of age-related neurodegenerative diseases and related neurological disorders in an increasingly elderly patient population

I previously suggested the following as a reason why this route may have been considered not viable using dopamine.

"maybe the pure amine solution may not be too stable. However even if you had to make a fresh solution every day, no big deal."

I found the following in SIGMA-ALDRICH literature,
" Storage/Stability
The free base of dopamine is very susceptible to
oxidation.6 Solutions at pH 5.4 to 6.8 have been
reported to be stable for 48 hours at 25 °C."

So at almost neutral, 6.8, ( neutral is pH 7), we could simply make up a fresh solution each day. Dopamine is very water soluble. Possibly we could make the solution just on the acid side 6.8, with say acetic or citric acid. It does not look like an insurmountable obstacle. Possibly it may be that the amine solution could be stabilised to oxidation by adding a water soluble antioxidant, for example vitamin C. Then a made up solution would last longer.
Ron

Ron, this is great! Why hasn't/haven't pharmas been working on this more recently? Perhaps we should look into patenting this ourselves....do you like how I phrased that? But seriously, if no one else is going to pursue this, why couldn't we do this ourselves or partner up with a company who sells/makes the inhaler that would be used? Or maybe a patent isn't even necessary, we just figure it out and start doing it! It sure beats a bunch of hit-or-miss pills every day with side effects, a hole in the gut for a tube, or brain surgery.

Hi Lurkingforacure,
You are very welcome to join the syndicate, free!!
However, I don't think WE can patent the idea, since it has been disclosed in public now, that prohibits patenting it. It is what is known as being in the Public Domain. I used to be in charge of patents at my former job.
What I find hard to understand is maybe there is a good reason why it has not been developed before, but if this is so, surely it would have been published somewhere by the researchers. Maybe Charlie is right and it may get into the bloodstream, but dopamine is already present as a natural compound in the body, where it acts as a hormone. This is compared to its action in the brain where it acts as a chemical messenger.
However, again, wouldn't the amounts be very small in the blood, assuming we only need a spray into the nose every couple of hours, using a dilute solution. Also, if it had been found to be a problem, wouldn't it have been reported somewhere.
You are very right, "It sure beats a bunch of hit-or-miss pills every day with side effects, a hole in the gut for a tube, or brain surgery. "
And you forgot injecting yourself with apomorphine!!
Ron

So, if it is effective (and I believe it would be), the profit would be in the delivery system. Now, being a mechanical system, it would be vulnerable to "tweaking" and spawning rapid competition, so it may not be as attractive as one might think from a corporate viewpoint. Unless the patent was broad enough.

However, according to the report, Kurve Technologies had such a system up and running in 2005. A little googling turned up a report that Kurve had "signed an agreement" with Schering-Plough in 2006 giving it exclusive rights to the technology. Four weeks ago, Schering-Plough announced major success with a new drug for PD with oral delivery. Development of a nasal delivery of dopamine would be in direct competition with the new product.

http://www.reuters.com/article/compa...ymbol=SGP_pb.N
(Note that there is no mention of nasal delivery with the other products.)

http://www.schering-plough.com/news/...?reqid=1013562

I don't want to be overly cynical, but....

OK, so we need to see exactly what is out there right now (no time at present for me since I have to go pick up my kiddos and once they are home nothing gets done) but even if there is something already out there, couldn't we either

(1) get them to join us in this quest (I know, ha, ha, ha);
(2) tweak the delivery system so it does NOT violate any patent they or anyone else may have
(3) forget tweaking, just mix the stuff up and try inhaling directly without an infuser or whatever they are called....sorry to be crude, but drug addicts do this all over the world every day and is seems to work (not speaking from experience, of course)
(4) more radical, and perhaps dangerous, take an asthma's inhaler and just use it for dopamine solution instead of putting the asthma medicine in (assuming that's how those things work, I don't even know but it has a certain appeal)-too crazy?

Thoughts?

I think the idea of the patented tech is that it gives greater control of dosage, which we may not need so much. If we can get the dopamine, a simple nose spray bottle would do it but it would require a very low-dose beginning. As was pointed out, too much dopamine has its own risks.

No Rick, you can't patent dopamine as such, maybe you would have a chance with your idea of a quick opening of the BBB and a shot of levodopa through the there for an instant hole. LOL
I wouldn't think there is any chance of us infringing any patents by simply making a stable solution of dopamine, putting it in an atomiser spray, and inhaling the fine mist through the nose. This would not need mega bucks of development. I already have a suitable spray.
If you could think of a significant improvement to this system, which is not in the literature,(in the public domain), and is not obvious from what is already known, that would be patentable. And it could be an improvement to the mechanical spray.
However, I am 72 and simply want the rest of my limited time easier than it is at present. Lets get the White Rat spirit back and suck it and see.
It may not work, but I can't see a reason why it shouldn't. We have tried dozens of ideas from banding to Rosemary essence to Ginko, so why not this?
Ron

I'm all for it - just let me know what to do!