Drug info - Methylone research

Discussion in 'Beta-Ketones' started by Alfa, Jan 8, 2005.

  1. Alfa

    Alfa Productive Insomniac Staff Member Administrator

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    Inhibition of plasma membrane monoamine transporters by beta-ketoamphetamines.

    Cozzi NV, Sievert MK, Shulgin AT, Jacob P 3rd, Ruoho AE.


    Department of Pharmacology, East Carolina University School of Medicine, Greenville, NC 27858, USA. [email protected]

    Methcathinone and methylone, the beta-ketone analogues of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA), respectively, were tested for neurotransmitter uptake inhibition in vitro. The beta-ketones were threefold less potent than the nonketo drugs at inhibiting platelet serotonin accumulation, with IC(50)'s of 34.6+/-4.8 microM and 5.8+/-0.7 microM, respectively. Methcathinone and methylone were similar in potency to methamphetamine and MDMA at catecholamine transporters individually expressed in transfected glial cells. For dopamine uptake, IC(50)'s were 0.36+/-0.06 microM and 0.82+/-0.17 microM, respectively; for noradrenaline uptake, IC(50) values were 0.51+/-0.10 microM and 1. 2+/-0.1 microM, respectively. In chromaffin granules, IC(50)'s for serotonin accumulation were 112+/-8.0 microM for methcathinone and 166+/-12 microM for methylone, 10-fold higher than the respective values for methamphetamine and MDMA. Our results indicate that methcathinone and methylone potently inhibit plasma membrane catecholamine transporters but only weakly inhibit the vesicle transporter.
     
    Last edited by a moderator: Jan 13, 2010
  2. Alfa

    Alfa Productive Insomniac Staff Member Administrator

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    Methcathinone and 2-methylamino-1-(3,4-methylenedioxyphenyl)propan-1-one (methylone) selectively inhibit plasma membrane catecholaminereuptake transporters.

    Nicholas V. Cozzi, Michael K. Sievert, Alexander T. Shulgin,* Peyton Jacob III,** and Arnold E. Ruoho
    Soc. Neurosci. Abs, 1998; 24: 381.8


    <HR>

    Abstract


    Methcathinone, the benzylic ketone analog of methamphetamine (MA), and methylone, the benzylic ketone analog of 3,4-methylenedioxymethamphetamine (MDMA), were synthesized and tested for their abilities to inhibit monoamine uptake in vitro. Methcathinone and methylone were threefold less potent than MA or MDMA at inhibiting [<SUP>3</SUP>H]5-HT uptake into human platelets, with IC<SUB>50</SUB>'s of 31.4 ± 7.3 mM and 5.8 ± 0.7 mM, respectively. In C6 glial cells stably expressing the rat dopamine transporter, methcathinone and methylone were similar in potency to MA and MDMA, with IC<SUB>50</SUB>'s for [<SUP>3</SUP>H]DA uptake of 0.36 ± 0.06 mM and 0.82 ± 0.17 mM, respectively. Methcathinone and methylone were also similar in potency to MA and MDMA in C6 cells expressing the human norepinephrine transporter, with IC<SUB>50</SUB>'s for [<SUP>3</SUP>H]NE accumulation of 0.51 ± 0.10 mM and 1.2 ± 0.1 mM, respectively. The benzylic ketone moiety of methcathinone and methylone had a large (tenfold) negative impact on the abilities of these drugs to inhibit the vesicular monoamine transporter (VMAT2) compared to MA and MDMA. In VMAT2-containing bovine chromaffin granules, the IC<SUB>50</SUB>'s for [<SUP>3</SUP>H]5-HT uptake were 103 ± 15 mM for methcathinone and 125 ± 16 mM for methylone. These results indicate that methcathinone and methylone are potent and selective inhibitors of plasma membrane catecholamine reuptake transporters, with more modest effects at the serotonin reuptake transporter. These drugs are essentially inactive at the vesicular monoamine transporter.
     
  3. Alfa

    Alfa Productive Insomniac Staff Member Administrator

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    Methcathinone (MCAT) and 2-methylamino-1-(3,4-methylenedioxyphenyl)propan-1-one (MDMCAT) inhibit [3H]serotonin uptake into human platelets.

    Nicholas V. Cozzi, Alexander T. Shulgin, and Arnold E. Ruoho
    Amer. Chem. Soc. Div. Med. Chem. Abs., 1998; 215: 152


    <HR>

    Abstract


    The benzylic ketone analogs of the psychoactive phenylisopropylamine methamphetamine (MA), MCAT, and of 3,4-methylenedioxymethamphetamine (MDMA), MDMCAT, were synthesized and compared to the nonketo compounds for their abilities to inhibit reuptake transporter-mediated [<SUP>3</SUP>H]serotonin accumulation into human platelets. MCAT inhibited [<SUP>3</SUP>H]serotonin uptake into platelets with an IC<SUB>50</SUB> of 33.7 ± 9.0 mM while MA exhibited an IC<SUB>50</SUB> of 11.7 ± 1.0 mM; this difference was not significant. The methylenedioxy-substituted compounds were about 6-fold more potent (p &lt; 0.05) than the unsubstituted compounds in this assay; MDMCAT displayed an IC<SUB>50</SUB> of 5.8 ± 0.7 mM and MDMA had an IC<SUB>50</SUB> of 2.1 ± 0.3 mM. The difference in potency between MDMCAT and MDMA was significant at p &lt; 0.01. These results indicate that beta-keto derivatization of psychoactive phenylalkylamines does not have a major impact on the drugs' ablility to inhibit serotonin uptake and that phenyl ring substitutions can enhance potency.
     
  4. HippieD9

    HippieD9 Gold Member

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    Could someone dumb this down a level for me? I'm just starting to learn about the actions of these drugs, and this seems rather interesting from what I can figure out.





    Thanks!


    D.
     
  5. Alfa

    Alfa Productive Insomniac Staff Member Administrator

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    Not completely or fully accurate dumbdown, but easier to understand: Methylone and Methcathinone are treefold less potent than MDMA and Meth in serotonine reuptake inhibition. Simular in potency in catecholamine, adrenalineand dopamine reuptake inhibition. Thus phenyl ring substitutions are more potent in serotonine reuptake inhibition, then ketones.


    It may also explain why methcathinone and methylone have dosage ranges of roughly 3 times as high then mdma and MA.Edited by: Alfa
     
  6. HippieD9

    HippieD9 Gold Member

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    Ok, I see now. So basically this helps support the 5ht (I think, this is off the top of my head) receptor theory for how these things work? Also good to know just cause of the possibility of other similar substitutions reacting similarly. THANKS!





    Peace,


    D.
     
  7. enquirewithin

    enquirewithin Gold Member

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    According to Erowid's reports methylone has doses similar to MDMA. What is an avererage dose?
     
  8. dr ACE

    dr ACE Titanium Member

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    form trip reports ive read it starts off at about 125-150mg and the highest ammount i read was 450mg but that sounded like it was almost an od situation..
     
  9. Peyote

    Peyote Gold Member

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    So its less bad for your brains than MDMA?? [​IMG]
     
  10. lociel

    lociel Newbie

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    I thinks so in my experience.
    but, i have done only "MDMA of tablet".
    When methylone of 200mg wastaken, i didn't feel damage like E-pills.
     
  11. Iggypoop

    Iggypoop Gold Member

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    With what alfa says ^^above^^ if you wanted to try and take enough methylone to produce the same serotonin 'type'effects as mdma you would be putting much more strain on your heart and dopamine system? What exactly are the effects from catecholamine reuptake inhibition?
     
  12. Iggypoop

    Iggypoop Gold Member

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    Methylone isn't a well researched chemical (like most rc's, including the one you are in love with) so you are always taking chances. Then again look at the guy who came up with these substances, Dr Shulgin, he's 79 i think and still going strong! If you don't take stuff all the time and do your research you'll be fine *not a guarantee* If you do a search there are plenty of posts on the forum, have fun![​IMG]


    Oh and someone on this site evaporated the liquid off 'explosion' and it yielded 240mg of powder, so its prolly somewhere in between 240-280mg.


    In my experiencemethylone doesn't give as much of a comedown as mdma, but thats just me, there are others who think its just as bad.Edited by: Iggypoop
     
  13. radiometer

    radiometer bananadine addict Platinum Member & Advisor

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    I wonder how much of the residue was methylone, though? SWIM's
    evaporated a little bit of explosion, and when dry it still smelled strongly
    of vanilla, and tasted like a mix of methylone and vanilla.
     
    Last edited: Mar 20, 2006
  14. nanobrain

    nanobrain Platinum Member

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  15. chico

    chico Iridium Member

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    This is an interesting article.


    However, I don't see any reference to Methylone. Is "Cathinone" a.k.a. Methylone? The more that I read the article, the more "Cathinone" started sounding like Methylone. Nonetheless, it never mentions the actual "Methylone" name, just Cathinone.
     
  16. radiometer

    radiometer bananadine addict Platinum Member & Advisor

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    No - this isn't the proper way to name it, but you could think of
    methylone as being 3,4-methylenedioxymethcathinone.
     
  17. radiometer

    radiometer bananadine addict Platinum Member & Advisor

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    Cool article, Nano, thanks.

    chico, from a quick glance it seems that they refer to methylone as MDMC
    in this document. Apparently they feel it is the proper way to name
    it. [​IMG]Edited by: radiometer
     
  18. chico

    chico Iridium Member

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    thanks radiometer.


    I was going to start looking around the Internet for "cathinone" to see if I could get my hands on some. It's nice to know that I have this stuff in my possession (Explosion).


    [​IMG]
     
  19. Alfa

    Alfa Productive Insomniac Staff Member Administrator

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    Methylone is not cathinone. As radiometer says it is 3,4-methylenedioxymethcathinone.Methylone(MDMC) relates to cathinone in the same way that MDMA relates to Amphetamine. MDMA, MDMC? Makes me wonder about MDMB. Did I miss something? lol. Edited by: Alfa
     
  20. chico

    chico Iridium Member

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    Ok, got it. Thanks for the clarification, Alfa.


    Still trying to get all these checmical structures down.