DL Phenylalanine: How does it work?

[ebola?]

they're vetted in peer review far more thoroughly than primary sources because they're lit reviews.

Oooh. I missed this initially. Lit reviews cannot be vetted more rigorously than the primary sources on which they depend, as all the information contained within depends on those sources. You have to put trust in the expertise of a single expert who has selected the relevant data. And sometimes, one ends up depending on mere 'experts'.

ebola

 

[Seppi]

Eh, I meant in terms of references/claims made from other papers. Primary sources very often cite others to make various statements, but this discussion/citation is secondary to the purpose of the paper in producing original research. Hence, cited claims don't justify extra scrutiny under normal circumstances.

 

[AlaskaThunder]

To the OP: I've been taking DPA (not DLPA or LPA) for a few years now. It can get expensive and is a little demanding (3x a day, empty stomach can be hard to do).
All I can offer you is my own anecdotal tidbits.

I forgo the L- isomer because I believe I read that 20% of the DPA turns into LPA within the body anyway, and DPA still noticeably elevates my mood/energy.

In my experience, combining DPA with an opiate/opioid does not make me any "higher", but the duration of the opiate lasts much longer, and seems to work better peripherally than centrally, which is fine by me. It works especially well for my arthritic-type pain in my lower back-pelvis region, and when I discontinue for a month, the pain slowly creeps back.

After taking DPA for 1 month or more, and then take some morphine, I don't have to redose the morphine for almost a whole day vs 6 hours w/o DPA. I would take DPA for that alone! haha!

Like anything else, not everyone will react the same. It works well for me, tho, and it may work well for you, too. There's just not a lot of information about DPA because of the lack of quality studies. The only way you'll know if it'll work for you is if you try it. Some people get nothing from it.

P.S. I'm really liking all the references!

 

[MartinFn]

Well guys,
it seems that this is exactly what i need, for mood lift and for fuckin terrible pain.. Some say it works fine, some it's nothing...well, i guess that if you don't try it, you can't find what it does...so i'm gonna try it, i'll go for the D-PA and i have a feeling that it will be awesome..i don't know, we'll see..
Hey Alaska my friend, your box is full, i tried to send you a PM and it says that you can't receive PMs, cause you have to clear it..I hope you're doing fine. Alaska..wow..only the name, making me feel the cold, it must be very difficult living there..
Anyway...%)



MartinFn

 

[AlaskaThunder]

Well guys,
it seems that this is exactly what i need, for mood lift and for fuckin terrible pain.. Some say it works fine, some it's nothing...well, i guess that if you don't try it, you can't find what it does...so i'm gonna try it, i'll go for the D-PA and i have a feeling that it will be awesome..i don't know, we'll see..
Hey Alaska my friend, your box is full, i tried to send you a PM and it says that you can't receive PMs, cause you have to clear it..I hope you're doing fine. Alaska..wow..only the name, making me feel the cold, it must be very difficult living there..
Anyway...%)



MartinFn

Sorry man! BL has some strange rules but I'm trying! Haha! Check again.

I hope it (the DPA) works for you. Keep us updated, yes?

It's...almost...summer...gah!!! What is that bright orb in the sky?? So bright...

 

[manoso]

L-phenylalanine significantly exacerbates tardive dyskinesia in schizophrenic patients:
http://www.ncbi.nlm.nih.gov/pubmed/9015796

Note that the dose in this study is extremely large - 100 mg/kg - so we can't NECESSARILY point to dopaminergic activity as being primarily responsible for this, since there are a lot of other things that could happen when you're taking that much phenylalanine. There could be all sorts of enzyme inhibitions or altered kinetics going on here. To draw a parallel, MDMA exhibits zero-order kinetics at high doses because it inhibits CYP2D6, which is also one of the primary enzymes responsible for metabolizing it. I'm not saying phenylalanine is inhibiting a decarboxylase enzyme or anything like that, I'm just pointing out that strange things often happen when you dose outside the "normal" range.

 

[ctambo]

Has anyone tried/read about the benefits of acetylphenylalanine (or N-Acetyl-D/L-Phenylalanine)? Since the half lives of DLPA is so long and bioavailability is so poor, it would be interesting if the N-acetyl version is faster-acting and active at lower doses (especially metabolism in to phenethylamine), just like N-Acetyl-L-Tyrosine or ALCAR. I found sources to buy, but no records of human use.

 

[DL-ark]

I've heard that DL-Phenylalanine is good for potentiating opiates but does it have to be DL? According to this thread it is just the dextro that inhibits endorphin breakdown. Is this true or is the levo enantiomer also needed for the inhibition of endorphin metabolism?

 

[ebola?]

Well, it probably doesn't actually work, so it doesn't matter what stereoisomer(s) you have. DL-phenethylamine will present the benefit of bioconversion into a maximal spectrum of metabolites. The levo-isomer is reasonably common in dietary protein, though not as common as, say, tyrosine.

ebola

 

[sekio]

Fucking amino acids, how do they work?

 

[Seppi]

L-phenylalanine significantly exacerbates tardive dyskinesia in schizophrenic patients:
http://www.ncbi.nlm.nih.gov/pubmed/9015796

Abnormal PEA metabolism is implicated in many different medical (psychological) conditions. I'm copy/pasting this from a post I made on a wikipedia talk page - these are quotes from reviews on TAAR1 and trace amines, some of which are focused on the relationship with their therapeutic potential.

References

• Berry MD (January 2007). "The potential of trace amines and their receptors for treating neurological and psychiatric diseases". Rev Recent Clin Trials 2 (1): 3–19. PMID 18473983.

  "changes in trace amines, in particular PE, have been identified as a possible factor for the onset of attention deficit/hyperactivity disorder (ADHD) [5, 27, 43, 78]. PE has been shown to induce hyperactivity and aggression, two of the cardinal clinical features of ADHD, in experimental animals [100]. Hyperactivity is also a symptom of phenylketonuria, which as discussed above is associated with a markedly elevated PE turnover [44]. Further, amphetamines, which have clinical utility in ADHD, are good ligands at trace amine receptors [2]. Of possible relevance in this aspect is modafanil, which has shown beneficial effects in ADHD patients [101] and has been reported to enhance the activity of PE at TAAR1 [102]. Conversely, methylphenidate, which is also clinically useful in ADHD, showed poor efficacy at the TAAR1 receptor [2]. In this respect it is worth noting that the enhancement of functioning at TAAR1 seen with modafanil was not a result of a direct interaction with TAAR1 [102].
  More direct evidence has been obtained recently for a role of trace amines in ADHD. Urinary PE levels have been reported to be decreased in ADHD patients in comparison to both controls and patients with autism [103-105]. Evidence for a decrease in PE levels in the brain of ADHD patients has also recently been reported [4]. In addition, decreases in the urine and plasma levels of the PE metabolite phenylacetic acid and the precursors phenylalanine and tyrosine have been reported along with decreases in plasma tyramine [103]. Following treatment with methylphenidate, patients who responded positively showed a normalization of urinary PE, whilst non-responders showed no change from baseline values [105]."

• Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375.

  "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...Both dopamine and 3-methoxytyramine, which do not undergo further N-methylation, are partial agonists of TAAR1 (TA1). ...
  
  TAARs as potential drug targets for the treatment of psychiatric disorders
  The dysregulation of TA levels has been linked to several diseases, which highlights the corresponding members of the TAAR family as potential targets for drug development. In this article, we focus on the relevance of TAs and their receptors to nervous system-related disorders, namely schizophrenia and depression; however, TAs have also been linked to other diseases such as migraine, attention deficit hyperactivity disorder, substance abuse and eating disorders [7,8,36]. Clinical studies report increased β-PEA plasma levels in patients suffering from acute schizophrenia [37] and elevated urinary excretion of β-PEA in paranoid schizophrenics [38], which supports a role of TAs in schizophrenia. As a result of these studies, β-PEA has been referred to as the body’s ‘endogenous amphetamine’ [39]"

• Sotnikova TD, Caron MG, Gainetdinov RR (August 2009). "Trace amine-associated receptors as emerging therapeutic targets". Mol. Pharmacol. 76 (2): 229–35. doi:10.1124/mol.109.055970. PMC 2713119. PMID 19389919.

  "Although the functional role of trace amines in mammals remains largely enigmatic, it has been noted that trace amine levels can be altered in various human disorders, including schizophrenia, Parkinson's disease, attention deficit hyperactivity disorder (ADHD), Tourette syndrome, and phenylketonuria (Boulton, 1980; Sandler et al., 1980). It was generally held that trace amines affect the monoamine system indirectly via interaction with plasma membrane transporters [such as plasma membrane dopamine transporter (DAT)] and vesicular storage (Premont et al., 2001; Branchek and Blackburn, 2003; Berry, 2004; Sotnikova et al., 2004). ...
  Furthermore, DAT-deficient mice provide a model to investigate the inhibitory actions of amphetamines on hyperactivity, the feature of amphetamines believed to be important for their therapeutic action in ADHD (Gainetdinov et al., 1999; Gainetdinov and Caron, 2003). It should be noted also that the best-established agonist of TAAR1, β-PEA, shared the ability of amphetamine to induce inhibition of dopamine-dependent hyperactivity of DAT-KO mice (Gainetdinov et al., 1999; Sotnikova et al., 2004).
  Furthermore, if TAAR1 could be proven as a mediator of some of amphetamine's actions in vivo, the development of novel TAAR1-selective agonists and antagonists could provide a new approach for the treatment of amphetamine-related conditions such as addiction and/or disorders in which amphetamine is used therapeutically. In particular, because amphetamine has remained the most effective pharmacological treatment in ADHD for many years, a potential role of TAAR1 in the mechanism of the “paradoxical” effectiveness of amphetamine in this disorder should be explored."

 

[Drink_Tea_Love_Cat]

what is the half life of DLPA?

having some mild negative effects on my heart and major anxiety, used it 84+ hours ago and quietly waiting to get better... would rather know how long I'm potentially waiting for than run off to the Dr and get blank faces or excessive testing

 

[d1nach]

Phenylethylamine and amphetamine are different then dpla. Is there any evodence that phenylalanine can cross the blood brain brainer and bind to taar receptors or that the body increases pea synthesis with extra phenylalanine orally?

 

[d1nach]

Btw seppi thank you i didnt know modafinil interacts with taar thats interesting because i like two drugs modafinil and amphetamine

 

[Morpheus19]

When increased PEA production is desired, D-phenylalanine (DPA) or D,L-phenylalanine (DLPA) is superior to L-phenylalanine, because DPA is readily decarboxylated to PEA, but can't be hydroxylated to tyrosine (Tyr). However, DPA is typically considerably more expensive than LPA and DLPA.

Is that true? Because in a rat study the following was concluded:

To confirm the finding that D-phenylalanine did not affect the content of beta-phenylethylamine, the metabolism of D-phenylalanine was examined using D-[14C]-phenylalanine. It was proven that D-phenylalanine did not convert to beta-phenylethylamine. On the basis of these findings the antidepressant effect of D-phenylalanine was critically discussed.

 

[Birdy-Num-Num]

All, grateful for your thoughts....if a decent dietary protein source (whey or pea protein) has those various aminos eg tyrosine , cystein , glutamate etc) in high doses, then will they get metabolised (absorbed and made useful) in same way as taking separate supplements? If so, is it therefore virtually pointless taking supplements....eg 50 grams of pea protein has circa 1.5 g of tyrosine which is more than enough.

though noticed they don't have L-Carnatine / ALC and other aminos including dlpa

THANKS