Ron, I could not help but notice the date on that publication was 2000-anything done on this since then? Why could not someone just get the pure dopamine and inhale it, determining for themselves how much is too much/too little-kinda like we do already but with Rx drugs. Since everyone is so different, that seems a perfect solution (no pun intended).

And where could one get pure dopamine anyway? Wonder how many neuros would be willing to write the script for this, it'd be like writing their own pink slip! Or am I missing something?

Hi Lurkingforacure,
There is a lot of work being done on this route. There is all the work by Bill Frey that Rick mentioned. As far as I know, dopamine is not a prescription chemical, but I may be wrong. It is a very simple chemical, and should be readily availabe and inexpensive.I can only think researchers are crossing every T and dotting every i before they try human trials. But why it has never been tried to the best of my knowledge, I don't know.
There are other medications delivered already by this nasal route via a simple aerosol nose spray. There has even been an international conference on nasal drug delivery. They sometimes call it intranasal.
I can't see many problems in using dopamine, except 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. This may be why it seems to be generally sold as the hydrochloride. But you could not use this, it would be very corrosive. It could be possible very prolonged nasal use of the amine may give sores on the nose lining, but wouldn't you think they would know by now!!!
It should at least offer potential as an occasional rescue spray. It would be better, faster than injecting your veins with apomorphine.
Ron

From a rather long article at:
http://www.reuniting.info/science/ar...lanotide_pt141

Can drugs increase sexual desire? Ever since Viagra, the pharmaceutical industry has been dreaming of the perfect aphrodisiac. Now, an American company may have developed a nasal spray that will do just that.

Prowling men and lascivious women, orgasms, odors and sports cars -- they're all nothing but molecules. Just like the world itself -- everything is made up of molecules.

No one knows that better than George Dodd -- indeed, he is a self-described marketer of molecules. He's also about to be the proud owner of a collection of molecules in the shape of a brand-new Jaguar XS in midnight blue with dark leather interior. And why not, he thinks to himself? After all, he's 63 and it's about time he spent some money. Besides, money is about to become plentiful in the life of the Irishman, a biochemist by trade. Dodd, who now lives in Scotland, has designed a brand new molecule.

The molecule Dodd has created resembles dopamine, a substance occurring naturally in the brain and which is associated with feelings of pleasure. Dodd's new product is intended to generate a healthy appetite for sex.

Mass production is already well underway, which explains the midnight blue Jaguar. It also explains why Dodd, on this day, is attending the International Conference of Sexologists in Lisbon. It's a four-day meeting of the world's leading experts on sex -- an assembly of those who seek to learn more about sex and provide mankind with more sex or better sex or just plain sex. And Dodd is now one of them. He's also interested in finding out what the competition is up to these days.....

I asked a couple of researchers at UCLA. My nextdoor neighbor is a researcher and they said, that it is a problem of side-effects. You cannot control the amount of DOpamine that gets into the bloodstream. It's the old BBB problem in reverse. This idea has been tried and rejected as unusable by researchers so you need to come up with a compound that will bind with dopamine and not let it be assimilated in the blood stream.


Charlie

Rick,
Some time ago I got a pile of Scentuelle patches and tried them, but they did absolutely nothing for PD symptoms.
We need dopamine.

Charlie,
I am not a medical doc, but when you sniff through the nose there is a direct connection into the brain. I think it is called the veronasal channel. Does it actually go into the bloodseream? It is the reason why smokers get an instant kick from their nicotine, and don't have to wait an hour for it to reach the brain via the blood like we do. The same is true of drug takers who snort their drugs, it gives an instant high.
I accept you can't control the level, but will it matter, will it just determine how long a particular sniff will last. Why don't we at least try a human trial. If the effect is instantaneous, like for smokers and drug takers,
when it wears off, you just take another sniff for instantaneous relief.
Don't forget, not only does the oral route take up to an hour to work, it is estimated that only a few % of the drug reaches the brain. most is destroyed en route. The nasal route delivers nearly 100%, one sniff could last a long time!!
Ron

the reason for my posting, is I watched a TV medical program, and they had twins that couldnt crawl by 9 months, the doctor later started the children on L-dopa...

Hypotonia means "low tone," and refers to a physiological state in which a muscle has decreased tone, or tension. A muscle's tone is a measure of its ability to resist passive elongation or stretching.

Description

Hypotonia is more a description than a diagnosis. It is most often seen in newborns (congenital) and infants, but it may persist through adolescence into adulthood. Another name for infantile hypotonia is "floppy baby syndrome." This refers to the tendency of a hypotonic infant's arms, legs, and head to "flop," or dangle loosely, when they are picked up or moved. In the past, the term "benign congenital hypotonia" was used for many cases in which no obvious cause for the hypotonia could be detected. Better diagnostic techniques and increased knowledge of neuromuscular disorders, however, have resulted in much less frequent use of this term.

Demographics

Hypotonia is the most common muscular abnormality seen in neonatal (newborn) neurological disorders. It affects males and females equally, and shows no preponderance in any particular ethnic group or race. An increase in the occurrence of hypotonia in recent years is correlated with increased survival rates of infants born significantly premature, since these children are at increased risk for neurological problems.

Causes and symptoms

The causes of hypotonia are varied and numerous. Some involve trauma to, or diseases of, the brain or spinal cord (CNS), while others affect the peripheral nerves, neuromuscular junction, or the muscles themselves. A disorder of the nervous system is a neuropathy, while a muscle disease is a myopathy. A neuromuscular condition is one in which a neurological disorder results in associated muscular symptoms.

CNS trauma and infection are perhaps the most common cause of hypotonia, both in infants and in children. Insult to the brain may occur prenatally (before birth), perinatally (around the time of birth), or postnatally (after birth).

Prenatal CNS damage may be caused by certain maternal/fetal infections, maternal diseases, problems with the placenta or umbilical cord, or maternal use of harmful substances such as alcohol or certain drugs. Most congenital brain malformations, however, have no discernible cause and are likely due to chance maldevelopment of a very complex organ. Perinatal asphyxia/hypoxia (lack of oxygen to the baby's brain) occurs less frequently than is commonly believed, but does present a risk for CNS damage that can result in hypotonia. The greatest risk for asphyxia/hypoxia is from complicated and/or premature deliveries. Infants who are born healthy may sustain post-natal brain injury if they suffer from breathing difficulties, develop an infection in the lining of the brain (see Meningitis), or suffer some other type of physical trauma or abuse.

While it is less common -

http://www.answers.com/floppy+baby+s...ookup&nafid=27

~~~~~~~~~~~~~~
article 2)

Aromatic L-amino acid decarboxylase deficiency
By

Keith Hyland
Disclosures:

Dr. Hyland receives a salary for his position as Director of Horizon Molecular Medicine.



Historical note and nomenclature
Disorders leading to severe deficiencies of biogenic amines (essentially, serotonin, dopamine, and norepinephrine) in infants and children were for many years primarily associated with biochemical defects of tetrahydrobiopterin metabolism (Hyland and Howells 1988; Hyland 1993). Tetrahydrobiopterin is the cofactor for tyrosine hydroxylase and tryptophan hydroxylase, the rate-limiting enzymes required for dopamine and serotonin biosynthesis. Deficiency of the cofactor leads to a marked decrease in the synthesis of the biogenic amine neurotransmitters (Butler et al 1978; McInnes et al 1984). Historically, children with these disorders were detected because tetrahydrobiopterin is also the cofactor for phenylalanine hydroxylase, so its absence leads to hyperphenylalaninemia, which is detected in neonatal screening programs. The inability to correct the neurologic symptoms with a low phenylalanine diet (Bartholome 1974; Smith et al 1975) led to the discovery of the tetrahydrobiopterin defects and the realization that the neurologic signs were essentially due to serotonin and catecholamine (dopamine and norepinephrine) deficiency within the central nervous system (Butler et al 1978).

The neurologic symptoms of biogenic amine deficiency in infants and young children with tetrahydrobiopterin deficiency are now well established and include hypersalivation, temperature disturbance, pinpoint pupils, oculogyric crises, hypokinesis, distal chorea, truncal hypotonia, swallowing difficulties, drowsiness, and irritability. In addition, there may be microcephaly, progressive neurologic deterioration, developmental delay, and convulsions (grand mal or myoclonic). In the neonatal period, abnormal signs include poor sucking, decreased spontaneous movements, and microcephaly (Smith 1990; Hyland 1993).

http://www.medlink.com/medlinkcontent.asp

AS I understand it, it does. it is my understanding that the area is so complex that it is impossible (improbable?) to not get the drug being applied into the blood stream as well as the brain.

Charlie

OK, here is why I would never be welcome as a medical/scientific participant, but I am not getting the problem with sniffing dopamine. If the concern is that you cannot regulate how much goes IN the brain, well, don't we already have that problem with sinemet? I mean, everyone's digestion and uptake is different, not to mention BBB porosity, so really, of a 25/100, they cannot really say with any certainty that all 100% of the 100mg levodopa makes it into the brain, nor any percentage of it, for that matter. So the "BBB problem in reverse" does not make a persuasive argument for me. And like Ron pointed out, if sniffing avoids the bloodstream, that's the whole point of it, why get bogged down with what might be floating around in the blood? Or, am I missing something (again)?

Then there is the point about not knowing how much to give-again, are we not already dealing with this already? Our neuro's response to most things is to either (1) up the dose or (2) change a med. He usually opts for upping the dose, and actually has given us permission to increase it ourselves "as needed", like many on this forum have. So we are already self-regulating, and self-administering, I do not see the problem here. I must be missing something huge.

Let me give it a try.
As I understand it, the "direct connection to the brain" through the nose is through receptor cells of some type (smell-associated?) in the nasal epithelium. Nerve fibers connected to those receptors finally end up connecting with the basal ganglia, which is the anatomical location of the substantia nigra, or SN. I think it is difficult, if not impossible for dopamine to travel backward all the way, through synapses in between, to the SN.
As we know, levodopa in the blood gets past the BBB into the (remaining, functional) SN cells through the same aromatic amino acid transporter system used to import phenylalanine and tyrosine. Dopa decarboxylase enzyme then converts it into dopamine inside the cells, where it is packaged in secretory vacuoles which are released in its neurotransmitter function.

Does this make sense?

Hi
here are a couple of papers to show intranasal route for dopamine works.....well if you are a rat!!
Ron, sorry about the wrong info. I am trying to find out where these investigators got their dopamine/

More later
Girija




: Eur J Pharm Sci. 2001 Aug;14(1):75-80.Click here to read Links
Levels of dopamine in blood and brain following nasal administration to rats.
Dahlin M, Jansson B, Björk E.

Department of Pharmacy, Division of Pharmaceutics, Biomedical Centre, Box 580, Uppsala University, SE-751 23, Uppsala, Sweden.

The aim of this study was to investigate the levels of [(3)H]dopamine in blood, the cerebrospinal fluid (CSF) and brain tissue samples in rats and to find out whether the drug is transferred along the olfactory pathway to the central nervous system following nasal administration. [(3)H]Dopamine (50 microCi) was given to male Sprague-Dawley rats either intravenously or nasally to the right nostril. For the absorption study, blood samples were withdrawn from the carotid artery. The CSF samples were taken by cisternal puncture and then brain tissue samples were excised. The presence of unchanged dopamine in the samples was ascertained using thin layer chromatography (TLC). The radioactivity in the samples was measured using liquid scintillation. The greatest amount of the total radioactivity absorbed from the nasal mucosa into the systemic circulation was observed at the first sampling point 15 min after administration. The bioavailability of the total radioactivity was 68+/-30%. The uptake of [(3)H]dopamine in the brain was significantly higher 30 min after nasal administration than after intravenous administration (P<0.01). TLC data showed that approximately 59%, 14% and 68% of the radioactivity in the olfactory bulb, CSF and olfactory mucosa, respectively, coeluted with dopamine. In conclusion, these results show that unchanged dopamine is transferred into the olfactory bulb via the olfactory pathway in rats.

Neuropsychobiology. 2008;57(1-2):70-9. Epub 2008 Jun 2.Click here to read Links
Behavioral actions of intranasal application of dopamine: effects on forced swimming, elevated plus-maze and open field parameters.
Buddenberg TE, Topic B, Mahlberg ED, de Souza Silva MA, Huston JP, Mattern C.

Institute of Physiological Psychology, University of Dusseldorf, Dusseldorf, Germany.

BACKGROUND: Recently, we found evidence that intra-nasally administered dopamine (DA), can enter the brain, leading to an immediate increase in extracellular DA levels in striatal subregions. This offers a potential alternative approach to target the brain with exogenous DA, which otherwise cannot cross the blood-brain barrier. Here, we examined whether intra-nasally applied DA also exerts behavioral activity on mesocortical and nigrostriatal dopaminergic functions. METHOD: Male Wistar rats (3-4 months) were tested for potential behavioral effects of intra-nasally applied DA (0.03, 0.3 or 3.0 mg/kg) in the forced swimming test (FST) for antidepressant-like activity, elevated plus-maze for anxiety-related behavior, and on motor activity in a novel and familiar environment. RESULTS: Intra-nasally administered dopamine in a dose of 0.3 mg/kg exerted antidepressant-like activity in the FST, but had neither anxiolytic-like nor anxiogenic-like effects in the elevated plus-maze. Furthermore, intra-nasal dopamine stimulated locomotor activity in a familiar, but not novel, open field. CONCLUSIONS: These results support the view that intra-nasally applied DA can act on the central nervous system by entering the brain via the nose-brain pathway, making this kind of application procedure a promising alternative for targeting the brain, and thus treating disorders involving mesocortical and/or nigrostriatal dopaminergic disturbances. 2008 S. Karger AG, Basel.

PMID: 18515976 [PubMed - indexed for MEDLINE]
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