Dopamine HCl blood brain barrier?

[LyCaNtHoR]

Does anyone know if it is possible to modify Dopamine HCl so it can be passed through the blood vessel brain barrier to allow it to reach neurons?

[Bandil]

Yes, methylate the -OH groups on the aromatic ring. However the result will not be dopamine and thus it is impossible.

I think an intercerebrospinal injection of dopamine is what you want  

[LyCaNtHoR]

[Vitus_Verdegast]

Methylating it will not help much, since 3,4-dimethoxyphenethylamine is completely inactive. I think this molecule is decomposed quickly by the body's MAO enzymes.

You can always try to brominate the latter though, it could be that 2-bromo-4,5-dimethoxyphenethylamine has some activity. We will not know until someone tries it out.

Or you could use the dopamine to inject Trichocereus cacti, as these will biosynthesize mescaline from it.

[Lilienthal]

Di-O-acetylation should do the trick. Alpha-methylation would help against premature degradation.

[Vitus_Verdegast]

But still wouldn't it be better to use injection as route of administration, certainly for the PEA and maybe also for the amphetamine?

I can probably assume that the di-O-acetyl analogs will not be more potent than 3,4-DMPEA/3,4-DMA ?

3,4-DMA should be a bit weaker than mescaline (observed logMU = -0.06, about equipotent as mescaline), while 3,4-DMPEA is quite a bit weaker (logMU = -0.67)

[M3Psych]

I think this molecule is decomposed quickly by the body's MAO enzymes.

L-Deprenyl would fix that.

[Vitus_Verdegast]

Seliginine (l-deprenyl) is a MAO-B inhibitor, like eg. yohimbine also is. For this purpose you'd need a MAO-A inhibitor, such as harmaline or a non-selective one like iproniazide. I would strongly recommend against doing such a thing, however.

[M3Psych]

Do you have a reference that yohimbine is any type of MAOI?

Also, MAO-B preferentially deaminates dopamine and phenethylamine. If this DA analogue is subject to oxidative deamination by MAO it would be MAO-B, not MAO-A. MAO-A preferentially deaminates norepinephrine, tyramine and tryptamines and is primarily found in the peripheary.

[Vitus_Verdegast]

When searching for the article that claimed this a while ago, I stumbled on this one:

However, we haven't seen any conclusive study on yohimbe and MAO inhibition. If yohimbe were a strong and definite MAO inhibitor, one would have to expect fatalities if the usual precautions against tyramine-containing foods were not heeded. Any herb that functioned as a definite MAO inhibitor would long ago have been classified as a poison. But yohimbe has been sold as a supplement for years. If incidences of death would have occurred after ingesting yohimbe because of yohimbe being a MAO inhibitor, it's unlikely this fact would not be reported widely. Alas, there are no widely circulating reports of yohimbe causing deaths because of its effects as MAO inhibitor.

http://www.yohimbe.org/chairmanmao.htm

Have there been any known trials with MAO-B inhibitors and dopamine or phenethylamine yet? It should be very interesting, but still I'd proceed with extreme care, starting with very low doses first.

[Lilienthal]

Vitus: The acetylated compound would be quickly desacetylated. If this happens after passing the BBB we have won    We could fine-tuni the desacetylation-halflife by using other (i.e. longer or branched) esters.

[M3Psych]

Well trials with MAOIs and DA would be useless, DA cannot cross the BBB. There have been limited trials w/ L-Deprenyl in combination with phenethylamine and L-Deprenyl with phenylalanine.

[Red_Crown]

3-hydroxy-L-tyrosine crosses the BBB and is promptly decarboxylated into dopamine.

It is used in the treatment of Parkinsonism along with carbidopa (a peripheral inhibitor of decarboxylation -- so the dopa isn't converted outside of the brain), and entacapone (an inhibitor of a step in dopamine breakdown).