Amino acids and the blood brain barrier

[CrimpJiggler]

I read that the blood brain barrier has a system which allows amino acids to pass. Its not just the 20 natural amino acids either because I know that l-dopa cross the BBB via this system. Does this apply to all amino acids? For example if you were to convert loperamides amide group into a carboxyl group, would the product be able to cross the BBB?

 

[nuke]

Pubmed is your friend
http://www.ncbi.nlm.nih.gov/pubmed/7861158

Simply changing one moeity in a giant compound will probably not at all make a transporter have high affinity for it. They generally only like things the size of amino acids and with "L-" stereochemistry.

 

[Hyperthesis]

One (albeit not the only) factor that influences BBB-passage are the exact pKa/pKb-values of the amino- resp. carboxyl-group involved. An example from the class of GABAergic ligands:
Muscimol: pKa1 = 4.8 | pka2 = 8.4
Piperidine-4-sulfonic acid (P4S): pKa1 = <1 | pKa2 = 10.3
GABA: pka1 = 4.0 | pKa2 = 10.7
All three compounds are very potent GABA-A-receptor agonists, but only the first one is active upon oral application. This can be explained easily by the ratio between ionized vs. unionized form, which depend on the shown pKa-values:
ca. 600 for muscimol (for the closely related thiomuscimol even as low as 13!)
800,000 for GABA
> 1,000,000 for P4S.
The lower the value, the more effective occurs BBB-passage.

With regard to loperamide *sigh!*: Neither are carboxylic ligands preferred by the opioid-receptors, nor is the idea of getting loperamide or a close relative into the brain very clever. Rather idiotic, I'd say.

 

[fastandbulbous]

Amino acids cross the BBB due to active transport (ie they have a specific carrier in the cell membrane which uses ATP in thr process of transferring it across. There's a masximum molecule size that fit in the transporter receptor and loperamide is too big; if it worked regardless of size then peptides would be actively transported across the BBB (and very few actually are)