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Any precursors for dopamine that work like 5-htp does for serotonin levels?

Discussion in 'Pharmacology' started by Synesthesiac, Feb 6, 2009.

  1. Synesthesiac

    Synesthesiac R.I.P.

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    Well the title says it all really. Are there any substances/supplements that you can take to raise your dopamine levels? I know that 5-htp works very well for some people by increasing serotonin levels and helping raise peoples mood, so is there a similar precursor for dopamine that would work in a similar way?
     
  2. EllisDee

    EllisDee Silver Member

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    L-tyrosine. The mechanism of L-tyrosine's putative antidepressant activity may be accounted for by the precursor role of L-tyrosine in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects.
     
  3. vinylmesh

    vinylmesh

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    L-dopa would be the equivalent of 5-htp. They use it for people with parkinsons. You need to have it prescribed, apparently it's not that safe.

    swim gets the impression that L-tyrosine would be the equivalent of l-tryptophan.

    http://en.wikipedia.org/wiki/L-dopa
     
  4. serpent

    serpent

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    ive been looking into this myself and decided to order some phenylalanine.my understanding is that this is metabolised to l-tyrosine which in turn is converted to dopamine.i was hoping to order some phenethylamine,but thanks to uk drug laws banning the basic buliding blocks of life i cannot.
     
  5. Lasha-Giorgi M.D

    Lasha-Giorgi M.D

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    L-tyrosine is a precursor of neurotransmitter dopamine, so theoretically taking l-thyrosine must increase dopamine level, well, SWIM is not sure if it will couse high but he is sure that taking l-tyrosine will rise the dopamine level. also note that l-tyrosine is not only dopamine's precursor but also to melanin. SWIM has never used l-tyrosine so he suggests being careful.
     
  6. Synesthesiac

    Synesthesiac R.I.P.

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    It seems like a lot of these substances come with various risks, so swim might leave them. But its all handy to know incase he decides to in the future. Many thanks.
     
  7. Alfa

    Alfa Productive Insomniac Staff Member

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    Mucuna Pruriens has a lot of L-Dopa, but you do NOT want a lot of dopamine in your body.
     
  8. Ilsa

    Ilsa Platinum Member & Advisor

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    ^^yep, pretty much:

    i attached an article on excess dopamine and psychosis; certain dopamine receptors have been heavily implicated in various types of psychosis and have also been linked to schizophrenia. just as too little dopamine results in movement disorder, too much can reult in psychosis and other cognitive issues. amino acid supplements are probably safe if taken as directed and even with a doctor's consultation to be extra safe. anything more drastic is pointless and potentially harmful.

    just an anecdote: this kid in maryland, a chem major, decided to do the home chemistry thing in 1976, accidentally synthesizing the neurotoxic compound MPTP while trying to synthesize the morphine-like opioid MPPP. MTPT is toxic to dopaminergic (dopamine producing) neurons, and within 3 days of injecting what he thought had been MPPP, he began exhibiting parkinsonism. the same thing happened abouta decade later when 7 people ingested MPTP-contaminated MPPP. this is a worst case scenario, just an interesting tidbit really and not all that related to the OP. but i think it's safe to say "if it ain't broke, don't fix it." ;)
     

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  9. Synesthesiac

    Synesthesiac R.I.P.

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    ^Thanks Isla,

    Yeah, I should clarify, I did not want to suggest that people take lots of substances that raise dopamine levels. I was just wondering if there were any safe and clinically tested methods that can regulate specific dopamine systems and give a type of anti depressant effect. Unlike the sertogenic system the dopamergic system is far more hazardous to mess with, involving things like neurotoxicity, and messing with peoples action-reward systems (which as pointed out above has been linked with shizophrenia/psychosis, and probably why so many people with shizophrenia smoke [but thats another issue completely])

    5-htp may very well work on the fundamentally basic level of 5-htp = more serotonin = elevated mood. But its certainly not as simple as more xxxx substance = more dopamine = elevated mood. Dopamine is far more precarious and not a system to be messed with lightly. Should have been more specific in the OP really, its really quite a vague question with a misleading implication.
     
    Last edited: Apr 28, 2009
  10. Jasim

    Jasim Gold Member

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    Swim has played around with mucuna pruriens before. He has to agree with what has already been said about attempting to increase dopamine levels. Any dopamine precursor supplement would disburse throughout the brain and you really don't want high levels of dopamine in some areas of the brain.

    Besides what has been said about schizophrenia and psychosis, dopamine also controls the nausea center of the brain.
    Trust swim, not fun. No good can come from it. Sounds like a good idea, but it really isn't.


    To answer the question of manipulating specific dopamine tracks...Not with a supplement. Drugs do that. And all the medications swim is familiar with that have such effects come with some really bad side effects (e.g. extrapyramidal).
     
    Last edited: Mar 17, 2009
  11. yulamada

    yulamada Silver Member

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    A little background info first:

    LD/CD - L-dopa/carbidopa are the active ingredients in the big pharma medications Sinemet, Parcopa and Atamet. These medicines are most often prescribed for Parkinson's Disease patients. The LD/CD combo prevents l-dopa transformation into dopamine within the body and limbs. Apparently l-dopa taken without carbidopa has been shown to have little effect on neurotransmitter levels, as the vast majority of LD will be turned into dopamine in muscle tissue before it can reach the blood brain barrier. 'LD' is also used as an abbreviation for the big pharma medication Levodopa, of which l-dopa is the single active ingredient. Carbidopa is also available on it's own as the single active ingredient in the medication Lodosyn.

    This Wiki snippet explains it well:

    "Used in tandem with L-DOPA (trade name levodopa, a dopamine precursor converted in the body to dopamine), it increases the plasma half-life of levodopa from 50 minutes to 1 1/2 hours. CarbiDOPA cannot cross the blood brain barrier, so it inhibits only peripheral DDC. It thus prevents the conversion of L-DOPA to dopamine peripherally. This reduces the side effects caused by dopamine on the periphery, as well as increasing the concentration of L-DOPA and dopamine in the brain."

    And now a subjective view on Mucuna Pruriens as a natural source of l-dopa vs. big pharma's synthetic sources of l-dopa. Mucuna pruriens is a novel leavy plant with vine like properties. It produces a leguminous like fruit, referred to as the Velvetbean. The bean itself is the main ingredient in mucuna pruriens powders and supplements. The beans are also roasted and ground for use as a coffee substitute.

    My badger's read extensively on l-dopa and mucuna pruriens in recent weeks; both anecdotal & scientific reports. Based on this reading, Mucuna pruriens standardized extracts, derivatives, and powders appear to have statistically significant different effects in Parkinson's Disease (PD) patients and placebo controlled human & non-human mammalian test subjects. Synthesized L-Dopa, on its own, has shown adverse reactions in much of its research, with mucuna pruriens intake showing little to no nastiness.

    Mucuna pruriens is not just a natural source of l-dopa. M. Pruriens contains over a dozen compounds that appear, via synergistic collaboration, to achieve blood-brain barrier penetration of l-dopa with minimal general body uptake. Nicotine is also one of the compounds in m. pruriens, leading some to believe it could prove effective in smoking cessation programs. The velvetbean is a potentially safer & more natural way to supplement the body with naturally occuring l-dopa, and in turn dopamine. It has been shown to provide a more balanced effect than big pharma's levodopa or levodopa/carbidopa products.

    M. Pruriens has been used in alternative treatments for a millenia in traditional medicinal practices (such as Aruyveda) in India and Africa. My four legged friend has read many many articles and stories detailing mucuna pruriens extensive history, and they have been largely positive. The same can not be said regarding the results of the lab synthesized variety of l-dopa, Levodopa - the most notable side effect being degenerative effects & desensitizing of dopaminergic receptors due to oxidative damage. Long term prescription & usage can cause the user to experience effects similar to opiate withdrawal and Parkinson's Disease, as well as manic episodes and compulsive risk taking behaviour.

    Mucuna pruriens has shown similar and greater efficacy relieving symptoms in PD patients than synthetic l-dopa medications; without the myriad side effects seen in long term usage of levodopa alone. Onset of symptom relief & peak plasma saturation of m. pruriens compounds was shown to be almost 50% more rapid than l-dopa alone. M. pruriens preparations have also exhibited the ability to mildly inhibit prolactin, increase testosterone, and result in higher levels of HGH secretion. As a side note, l-dopa can cross the blood brain barrier via a different ion channel than most essential aminos, bypassing the 'bottleneck' other endorphin precursors must contend with. This, no doubt, is one of the reasons both natural & synthetic sources of l-dopa have such an expedient effect.

    Strict comparisons of m. pruriens & l-dopa are like comparing eating a orange to taking vitamin C supplements. Despite sharing a similarity, they are quite different.

    Lastly, taking l-tyrosine (the amino acid precurcursor which converts into l-dopa within the body) will not necessarily come to the same result as taking m. pruriens. The body still requires properly functioning enzymatic machinery to convert l-tyrosine to l-dopa. In certain individuals (like PD patients) this enzymatic activity is failing, and is the reason l-tyrosine supplementation does not work well for said patients. L-tyrosine is 2 steps away from becoming and an endorphin, whereas l-dopa (from either source) is only 1 step away from morphing into it's neurotransmitter roles.

    I'm not doctor, or even post-grad biology guru, so flame on if SWIM is mistaken or not on the right track. The more info the better for us all to make educated decisions. Would love to here commentary from SWIY that has experience in chemistry or a possibly a degree in relevant biological studies.
     
    Last edited: Apr 16, 2009
  12. rocknroll714

    rocknroll714

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    L-Phenylalanine -> L-Tyrosine -> L-DOPA (Levodopa) -> Dopamine

    L-Phenylalanine and L-Tyrosine can be purchased at any vitamin store like GNC or the Vitamin Shoppe. L-DOPA can only be obtained via prescription, the internet, or in the plant Mucuna Pruriens. It's recommended to take L-DOPA only with a peripheral dopa decarboxylase inhibitor such as carbidopa to prevent premature conversion in the periphery, but it's not really necessary. Hope that helps.
     
    Last edited by a moderator: Sep 3, 2012
  13. eche05

    eche05

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    SWIM has bought L-Tyrosine a few months ago, it worked great. He reported a similarity to that of 10-20mg of IR dextroamphetamine.

    The method of action is pretty straight-forward.

    L-Tyrosine ---(tyrosine hydroxylase)--> 3,4-dihydroxy-L-phenylalanine or L-DOPA ---(dopamine-beta-hydroxylase)---> Dopamine ---> Norepinephrine* eventually.

    *(The method of action is intertwined with post-synaptic alpha-adrenergic release of)norepinephrine.
     
  14. Pharmer John

    Pharmer John Newbie

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    l-phenylalanine is probably your best bet, it is a essential amino acid to boot.
     
  15. rocknroll714

    rocknroll714

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    I vouch for L-phenylalanine as well. Unlike L-tyrosine and L-DOPA, it partially metabolizes into PEA which is a potent amphetamine-like stimulant. L-phenylalanine also takes longer to come up but it lasts longer too which is another plus.
     
    Last edited by a moderator: Sep 3, 2012
  16. surgery_x

    surgery_x

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    I would like to shed some light on the subject. L-Tyrosine, while not being converted into PEA - an amphetamine like substance - tyrosine still retains the ability to be converted into 3,4-dihydroxy-L-phenylalanine (L-DOPA), and thus dopamine and epinephrine etc. Pharmacologically, L-phenylalanine is hydrolized (addition of a -OH hydroxy functional group at the 3 and 4 position on the carbon ring). L-Phenylalanine is also, unfortunatly, metabolized into PEA which only temperarily increases dopamine - while depleting dopamine-releasing cortical density over time, similar to cocaine or methamphetamine.

    In short, L-Phenylalanine is comparable to heroin (more potent, but more damaging metabolites) while L-Tyrosine is comparable to morphine (some risk, but better controlled, and more research performed about dosage and longitudal studies).

    Here's some info I found:

    ===========================================================

    Small double-blind, comparative studies suggest (but do not prove) that both the D- and DL- forms of phenylalanine might be helpful for depression.[2,3 ]

    Weak and contradictory evidence has been used to advocate the use of D-phenylalanine as a general analgesic (pain relieving treatment)[.4-7 ]

    Preliminary uncontrolled and double-blind studies found that L-phenylalanine may enhance the effectiveness of ultraviolet for vitiligo.[8-10 ]

    Highly preliminary evidence suggests that D-phenylalanine may be helpful for multiple sclerosis when combined with transcutaneous electrical nerve stimulation (TENS).11 D-phenylalanine has also been proposed as a treatment for Parkinson's disease (but see Safety Issues below).[12 ]

    Although D- and DL- phenylalanine are marketed as treatments for attention deficit disorder, they do not appear to be helpful.[13,14] Some proponents claim that phenylalanine works better when combined with tyrosine, glutamine, and gamma-aminobutyric acid (GABA), but this has not been proven.


    =============================================================


    Unfortunately, there have not been any double-blind, placebo -controlled studies of phenylalanine for depression. This is too bad, since without such evidence we can't be sure that the supplement is actually effective.

    L-Phenylalanine seems like a short term suppliment, but there hasn't even a few double-blind placebo-controled studies - thus making me vouch for L-Tyrosine overall.

    (BTW I can't post link, as I do not have the minimum 50 posts. Sorry.)
     
  17. rocknroll714

    rocknroll714

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    DL-Phenylalanine (DLPA) is the best if you ask me. The D-isomer acts as an enkephalinase inhibitor and prevents the breakdown of the endogenous enkephalins in your body which bind to the delta-Opioid receptors, while the L-isomer metabolizes into dopamine and beta-phenethylamine (PEA). The enkephalins build up and you get a mild opiate buzz after a few days, plus of course the stimulant effects. By the way in response to the above poster, as far as I know PEA isn't toxic, but I could be mistaken. It certainly seems to be much less toxic than amphetamine or methamphetamine from everything I've heard anecdotally.
     
    Last edited by a moderator: Sep 3, 2012
  18. Sloop

    Sloop

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    L dopa, l tyrosine, DL or just L ? phenylalanine sure

    assuming the availability of these substances is the rate limiting factor for instance their is a fair bit of literature out there that they only work on dopamine type depressed people and then at a low rate of reponse

    there is quite a few other substances like zinc B6 etc involved in the enzymatic conversion of these substances to dopamine that on the modern western diet are possibly more limiting on the rate of conversions of precurssors to dopamine.

    As an older adult with ADHD that eats well sleeps well and pays attention to exercise I found these subtsances did little even when I felt a bit burnt out from medical stimulants, which appears to be the case with most ADHD sufferers. As pointed out it is the place of dopamine enhancement in the brain and not the amount overall that makes a difference for most people with minimal or no clear cut brain disorders and this requires a different pharmacological approach. Fro experience I have found just adding more dopamie can make you feel like shit sometimes. As can just adding a receptor agonist though sometimes I find dopamine recptor agonists a little useful like piribedil, bromociptine dostinex and even more so drugs that clear the path for dopamine function in the right parts of the brain such as tianeptine, offcourse nothing matches a good dose of dexedrine or ritalin etc

    and if you are eating and sleeping well and exercising well you seldom get burnt out after years of medical stimulant use.

    I know this is not directly answering your question, but it is important background I suspect

    regards
    Sloop
     
  19. Ilsa

    Ilsa Platinum Member & Advisor

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    [​IMG]



    actually, l-tyrosine is hydroxylated, not hydrolyzed, to form dihydroxyphenylalanine (L DOPA). hydroxylation indicates addition of an hydroxyl (OH-) group while the latter indicates cleaving of a water molecule into its component parts: H+ and OH-.

    the net result is correct and , but if one is going to talk chemistry, be sure they have a firm handle on the terminology, as th edevil is in the details and one wrong bond and one could be dealing with an entirely different compound.

    PEA = ? what does what does this stand for? phenylethylamine? that would be a reasonable assumption but, the full name of the compound should be given for the sake of anyone who is unfaamiliar with the subject matter.

    as far as the amino acids mentioned and their effects versus the drugs mentioned and their effects, that comparison is between two things that are incomparable. not quite apples and oranges, but maybe like mammals: elephants and mice. so, what point do you want to express with this? Please describe more fully how tyrosine and phenylalanine compare




    can you list the journal, authors (first is most helpful in terms of finding the article), year published, volume and issue numbers? if i have those (or most of them) i can likely find and upload it. this article looks promising, thanks for bringing it into the discussion. Am not trying to be harsh, this is a decent post and with a little more detail it will be much more meaningful...apologies for my atrocities in spelling and probably grammar--not enough sleep! ;)
     
    Last edited: Apr 28, 2009
  20. Gradient

    Gradient Chem|EB|DMT Staff Member

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    Sorry, it appears that there is a limitation on the size of thumbnails. Perhaps if you download it and enlarge it with whatever image viewing program you have, it wont break down too badly.
     

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