TAAR1's role in the pharmacodynamic actions of Trace-Amines/Phenethylamine-Derivative

[ebola?]

N-methylphenethylamine is endogenous and produced by Phenylethanolamine N-methyltransferase with PEA as a (high affinity) substrate

Is this confirmed via research detailing binding affinities?

ebola

 

[h3lp]

Here are the results of my research.

"Trace amines (TAs) such as p-tyr, β-phenylethylamine, octopamine, and tryptamine are metabolites of amino acids that are found at low concentrations in the brain"

Thus TA's such as β-phenylethylamine and tryptamine can be found in miniscule amounts under control conditions within the brain.

"While several TAARs were identified, only TAAR1 and, to a lesser extent, TAAR4 respond to typical TAs (5). TAs such as p-tyr and β-phenylethylamine activate human, mouse, and rat TAAR1 with EC₅₀ values of 0.2–1.7 μM. Other TAs (octopamine, tryptamine), classical biogenic amines, and amphetamine-related psychostimulants have much reduced potency and efficacy at TAAR1."

Here we can deduce that TAAR1 and TAAR4 respond to trace amine but TAAR1 to a greater extent assuming said TA's are typical in variety.

We can also see that β-phenylethylamine activates at TAAR1 with EC₅₀ values of 0.2–1.7 μM, however tryptamines and amphetamine related psychostimulants have redunced pottency and efficiency at TAAR1 meaning one could expect little to no result.

"This resulted in the identification of the TAAR1 antagonist EPPTB (Fig. 1). EPPTB potently antagonized cAMP production induced by activating mouse TAAR1 with 1.5 μM β-phenylethylamine (IC₅₀ = 27.5 ± 9.4 nM"

Here we can see β-phenylethylamine at 1.5 μM had cAMP production potently antagonized by TAAR1 antagonist EPPTB.This production was activated with β-phenylethylamine further empasizing its relationship with TAAR1.

Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785295/

 

[Seppi]

Is this confirmed via research detailing binding affinities?

ebola

Not sure I've read a paper detailing affinities of PNMT substrates, though I know that measurement isn't required for confirming substrate activity.
Both papers I cited include it in their metabolite graphic for trace amines, but the Renaissance paper states: "In addition to the main metabolic pathway, TAs can also be converted by nonspecific N-methyltransferase (NMT) [22] and phenylethanolamine N-methyltransferase (PNMT) [23] to the corresponding secondary amines (e.g. synephrine [14], N-methylphenylethylamine and N-methyltyramine [15]), which display similar activities on TAAR1 (TA1) as their primary amine precursors."

I've found it virtually impossible to find some of the derivative trace amines in metabolome databases. In any event, since both of those papers are reviews, the answer to your question might be in one of the associated primary references of those 2 papers. I don't have time to check atm though.

 

[ebola?]

Highly relevant, thanks.

ebola

 

[Lightning-Nl]

Highly relevant, thanks.

ebola

He's one of the moderators for the Wikiarticle