(In response to ND) I completely get what your saying, and I'll admit pharmacology is not one of my strong points, I'm an organic chemistry student, and my interest here was purely structural, (I don't mean to sound like a pretentious nit-picker here, but it's a N-methyl-phenethylamine moiety found in LSD, it's a methyl group short of meth amphetamine), I'm completly certain that pharmocologically it would be a useless endeavor to put two methyl groups on nitrogen 6 of LSD, but structurally it creates a burried DMT moiety within the compound, which was the initial concept.
(Position 6 on LSD is a pharmocologically "hot" spot to tinker with, the xxx-LAD series involves dealkylating nitrogen 6, giving nor-LSD, then adding alkyl substituents to nitrogen 6, altering its pharmacological action, so, an ethyl group at nitrogen 6 Gives ETH-LAD, a propyl chain gives PRO-LAD, ans allyl chain gives AL-LAD, etc...
So I'm sure my concept compound would still have some interesting activity, though as I said, pharmacology is not one of my strong points, I'm a chemistry person.
The pharmacological information you mention does interest me, it was just some what peripheral to the initial concept...
It was novel moiety combination in structures of known compounds that was fascinating to me.
This is the shared pharmacology of the psychedelics as I understand it, though there is partial agonism here and there, which I'm sure is mentioned in your paper, which I can't get to work (I'm on an old device)
·psychedelic phenethylamine compounds ( 5ht2a and 5ht2c receptor agonism)
·psychedelic tryptamine compounds ( agonism at 5ht1a + 5ht2a + 5ht2c )
Then there's LSD (5ht1a + 5ht1b + 5ht1d + 5ht2a + 5ht2c + 5ht5a + 5ht6 + 5ht7 + d1 + d2 + d3 + d4+ Alpha-2 )
David E. Nichols says LSD has "rich" pharmacology due to the many receptor sites it's agonizes, fascinating stuff...
I'll look into that paper, I'll try to find a way to get it to work.
This link (below) shows the N-methyl-phenethylamine moiety (right) and the mono-methyl-tryptamine moiety (left) burried within LSD
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I was researching quaternary ammonium cation compounds in relation to DMT when I came across shulgins methods for synthesis of DMT:
(He is creating a quarternary ammonium cation of DMT (N,N,N-trimethyltryptammonium iodide) with tryptamine and methyl iodide, and then demethylating it into DMT!
Here's the entry from TIHKAL:
SYNTHESIS : (from N,N,N-trimethyltryptammonium iodide, dimethyltryptamine methiodide, DMT·CH3I): This quaternary salt is prepared from tryptamine and methyl iodide. To a stirred solution of 3 g tryptamine in 30 mL IPA there was added 10 g methyl iodide. Cream-colored solids appeared immediately and, after 12 h stirring at room temperature, these were removed by filtration, washed twice with IPA and warm isopropanol, and air dried to constant weight. There was thus obtained 1.81 g N,N,N-trimethyltryptammonium iodide. Recrystallization of an analytical sample using acetonitrile gave a white crystalline product with a mp of 210-211 °C. IR (in cm-1): 767, 919, 953, 978, 1105, with a sharp stretch at 3400. In principle, DMT is contained in the filtrate along with NMT and tryptamine itself. The tryptamine can be removed based on its ether insolubility and the NMT by its conversion to the benzamide with acetic anhydride or benzoyl chloride. The remaining basic material is largely DMT which can be further purified as the picrate salt. The yield is minuscule, and better results are obtained by the demethylation of this salt.
The demethylation of the iodide salt: Under an inert atmosphere, a solution of 0.40 g N,N,N-trimethyltryptammonium iodide in 5 mL THF was treated with 1.5 mL of 1M LiEt3BH in THF and held at reflux temperature for 9 h. After cooling, the mixture was acidified with dilute HCl and the THF removed under vacuum. The residue was suspended in dilute NaOH and extracted with Et2O. The extracts were pooled, and the solvent removed under vacuum to provide a residue of 0.12 g N,N-dimethyltryptamine (DMT) as a crystalline solid, with a mp of 57-59 °C. IR (in cm-1): 732, 740, 811, 859, 1011, 1037, 1110, 1171. The MS is discussed below.
The demethylation of the chloride salt: A hot aqueous solution of N,N,N-trimethyltryptammonium iodide was treated with an excess of freshly precipitated AgCl, and all was boiled gently for 15 min. The mixed silver halides were removed by filtration, and the filtrate stripped of H2O as rapidly as possible. To the residue there was added a small amount of MeOH follow by acetone until the crystallization of N,N,N-trimethyltryptammonium chloride was complete. It had a mp of 193 °C (80%), and it is considerably more water soluble than the starting iodide. This salt was pyrolysed under hard vacuum and the residue distilled. This distillate was dissolved in a small amount of methanol and acidified with dilute nitric acid. A small amount of insoluble material was removed by filtration, the aqueous phase washed with CHCl3, made basic with aqueous NaOH, and extracted with CHCl3. The solvent was removed under vacuum, and the residue treated with a hot solution of picric acid. This was decanted from a little insoluble material, and slowly cooled to provide the picrate of DMT as yellow needles with a mp of 167 °C. An aqueous suspension of this picrate was made basic with an excess of aqueous NaOH, extracted with Et2O, and the solvent removed under vacuum to provide a pale yellow residue that crystallized. This was pressed on a porous plate and washed with petroleum ether to give N,N-dimethyltryptamine (DMT) as an off-white solid with a mp of 47 °C.
The demethylation of the thiophenolate salt: A suspension of 2.5 g N,N,N-trimethyltryptammonium iodide in 25 mL MeOH was brought into solution by heating, and treated with 1.0 g Ag2O. The mixture was heated for 10 min on the steam bath, the solids removed by filtration and washed with an additional 20 mL MeOH. The methanol solutions were treated with 1.0 g thiophenol and the solvent was removed under vacuum. The resulting viscous oil (2.12 g) was heated with a flame to the reflux point and there was extensive bubbling. After 5 min, the light colored reaction mixture was cooled to room temperature, dissolved in 50 mL CH2Cl2, and extracted with two 25 mL portions of dilute HCl. These were pooled (pale yellow color), made basic with 5% aqueous NaOH and extracted with 3x25 mL CH2Cl2. After removal of the solvent from the pooled extracts, the residue (an amber oil, 1.04 g) was distilled at the KugelRohr. A white oil distilled over at 130-140 °C at 0.1 mm/Hg, and crystallized spontaneously. This distillate weighed 0.77 g, and was recrystallized from boiling hexane after decanting the solution from a small amount of insolubles. There was thus obtained 0.40 g of dimethyltryptamine (DMT) with a mp 67-68 °C. The distillate contained about 3% of 2-Methyl-1,2,3,4-tetrahydro-b-carboline (parent peak mass 186, major peak mass 186) as an impurity which was lost upon recrystallization. -shulgin; TIHKAL
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This is getting to long so I will respond to other posts in another post.
-EG
