N -Methyltryptamine

Girgensohnia spp. G. diptera Bge. contains N-methylpiperidine and dipterine, CHH14N2, m.p. 87-8°, [a]D 0° hydrochloride, m.p. 177-8°, picrate, m.p. 189-190°, and picrolonate, m.p. 242-3°, which was later shown to be N-methyltryptamine.i G. oppositiflora Pall, contains N-methylpiperidine and girgensonine, C13H13ON2, m.p. 147-8°, [aJjj 0°. The latter forms a hydrochloride, m.p. 145-8°, and a picrolonate, m.p. 192-4°, and on hydrolysis by alkali yields piperidine, hydrocyanic acid and p-hydroxybenzaldehyde, indicating that it is N-piperidyl-p-hydroxy-phenylacetonitrile, and this has been confirmed by comparison with a synthetic specimen. ( (1) Juraschevski and Stepanova, J. Gen. Chem. Russ., 1939, 9, 2203 Juraschevski, ibid., 1940, 10, 1781. (2) Juraschevski and Stepanova, ibid., 1946, 16, 141). 

Misztal (148) prepared 5-methoxy-N-methyltryptamine (5-OMeN-MeT 36) for the purpose of pharmacologic evaluation, but no data were reported. Smythies and co-workers (210) reported that 5-OMeN-MeT was much less active than either DMT or 5-OMeDMT in disrupting the conditioned avoidance response in rats. Taborsky and Mclsaac (229) also found 5-OMeN-MeT to be less active than 5-OMeDMT. These latter authors further demonstrated that 5-OMeN-MeT was rapidly and nearly quantitatively metabolized by MAO to 5-meth-oxyindole acetic acid. Julia and Manoury (123) investigated 5-methoxy and... 

Alpha-methylation of DMT reduced its behavioral activity in animals, while alpha-methylation of N-methyltryptamine (27) resulted in an agent with stimulant properties (137,228). Alpha-methyltryptamine (a-MeT structure 77), however, is hallucinogenic in man at doses of about 30 mg. Thus it is two to three times more active than DMT (for review see refs. 24, 81, and 196). 5-Methoxy-a-methyltryptamine (5-OMe-a-MeT 78) was also determined to be twice as active in man as its dialkyl counterpart, 5-OMeDMT. In human trials, 5-OMe-a-MeT produced behavioral effects at about 3 mg (204). A comparison of the activities of the individual isomers of 78 in man has not been reported. However, Glennon and co-workers (76,83,90) found that the (+)-isomers of both a-MeT and 5-OMe-a-MeT are more active than their racemates in tests of discriminative control of behavior in rats. Although (+)-5-OMe-a-MeT was four times more active than its enantiomer, (-)-a-MeT did not produce effects similar to either racemic a-MeT or 5-OMeDMT. 

N-Monoalkyltryptamines are another group of agents that have not received much attention. N-Methyltryptamine (27) and its 5-methoxy derivative 36 have been detected as constituents of plant materials used by certain South American Indians as hallucinogenic snuffs (109). Because these plant materials are also known to possess the established hallucinogens N,N-dimethyltryptamine (DMT 37) and 5-OMeDMT and since neither N-methyltryptamine (27) nor 5-methoxy-N-methyltryptamine (36) has been studied in the pure form, the effect of these latter two agents in man is presently unknown. 

N-Methyltryptamine (27) was found to have no effect on the acquisition of avoidance behavior (240). Brimblecombe (23) compared the behavioral effects of a series of N-monoalkyltryptamines and N,N-dialkyltryptamines using Hall s open-field test. Although there was no clear-cut structure-activity relationship,... 

Other methylated tryptamines with similar action to 5-fluoro-a-methyltryptamine are 6-fluoro-a-methyltryptamine, 7-methyltryptamine, N-methyltryptamine, 5-methyltryptamine. The dosages will also be much the same. Some non-methylated derivatives are claimed to be active, but I could not find dosage or explicit effects. They are 5-fluorotryptamine, 6-fluorotryptamine, 5-and 6-fluorotryptophans. Alpha-methyltryptamine may be legal in some states and is claimed to give a 16 hour trip with oral doses of 30 mg. Look for these tryptamines in Chemical Sources to find the supplier that sells them and call to get prices. Never ask them about the doses or effects in any correspondence. 

The demethylated homologue is N-methyltryptamine (NMT) and it is also widely distributed in nature. It has a synthesis in an entry of its own. 

Norbufotenine (5-hydroxy-N-methyltryptamine, N-methylserotonin, 5-OH-NMT) This base is scattered in both the animal and the plant kingdoms. It has been found in quite a few toads and in barley shoots. It has been isolated from the herb Desmodium pulchellum. This is an interesting twilight compound lying halfway between a notorious toxin (bufotenine) and a vital neurotransmitter (serotonin). And it is unexplored, for shame. It has been detected in the urine... 

TRYPTAMINE, N-ETHYL-4-HYDROXY-N-METHYL 4-INDOLOL, 3-[2-(ETHYLMETHYLAMINO)ETHYL] N-ETHYL-4-HYDROXY-N-METHYLTRYPTAMINE 3-[2-(ETHYLMETHYLAMINO)ETHYL]-4-INDOLOL... 

TRYPTAMINE, N-BUTYL-N-METHYL INDOLE, 3-[2-(BUTYLMETHYLAMINO)ETHYL] N-BUTYL-N-METHYLTRYPTAMINE 3-[2-(BUTYLMETHYLAMINO)ETHYL]-INDOLE... 

A structural isomer has been made, with the butyl group branched at the nitrogen atom. This is N-s-butyl-N-methyltryptamine, or MSBT. It came from a two pass alkylation of N-methyltryptamine (NMT) with s-butyl bromide in isopropylalcohol in the presence of solid potassium iodide. It remained an oil, but was over 90% pure by GCMS, with unreacted NMT being the major impurity. MS (in m/z) C6H14N+ 100 (100%) indolemethylene+ 130 (8%) parent ion 230 (1%). It has been assayed in man, but it remains an unknown. 

A suspension of 0.76 g LAH in 50 mL THF was stirred under an inert atmosphere, and treated with the dropwise addition of a solution of 2.5 g N-(benzyloxycarbonyl)-4-methoxytryptamine in 30 anhydrous THF. The reaction mixture was held at reflux for 30 min, then cooled to 40 °C and the excess hydride destroyed with the addition of 50% aqueous THF. The solids were removed by filtration, washed with THF, the filtrate and washings combined, and the solvent removed under vacuum. The residue, impure 4-methoxy-N-methyltryptamine, was dissolved in 50 mL ethanol, treated with 1.0 mL acetone, then with 0.5 g 10% Pd / C, and the reaction mixture shaken under a hydrogen atmosphere at 50 psi for 15 h. The catalyst was removed by filtration through a bed of Celite, the filtrate stripped of solvent under vacuum, and the solid residue recrystallized from Et20 / hexane to give 0.51 g 4-methoxy-N-methyl-N-isopropyltryptamine (4-MeO-MIPT) which had a mp 80-81 °C. Anal C15H22N20. C,H,N. MS (in m/z) C5H12N+ 86 (100%) indolemethylene+ 160 (4%) parent ion 246 (6 %). 

SYNTHESIS To a solution of 1.40 g 5-methoxy-N-methyltryptamine (5-MeO-NMT. see separate recipe) in 50 mL methanol there was added 1.0 mL acetone and 0.5 g 10% Pd / C. This mixture was shaken under a hydrogen atmosphere at 50 psi for 15 h. The catalyst was removed by filtration through a bed of celite, the filtrate stripped of solvent under vacuum, and the solid residue recrystallized from Et20 / hexane to give 1.45 g N-isopropyl-5-methoxy-N-methyl-tryptamine (5-MeO-... 

TRYPTAMINE, 5,6-DIMETHOXY-N-ISOPROPYL-N-METHYL INDOLE, 5,6-DIMETHOXY-3-[2-(ISOPROPYLMETHYLAMINO)ETHYL] 5,6-DIMETHOXY-N-ISOPROPYL-N-METHYLTRYPTAMINE 5,6-DIMETHOXY-3-[2-(ISOPROPYLMETHYLAMINO)ETHYL]INDOLE... 

A well-stirred suspension of 0.55 g LAH in 25 mL anhydrous THF was treated, dropwise, with a solution of 0.53 g 5,6-dimethoxy-N-isopropyl-N-methylindoleglyoxlamide in 75 mL anhydrous THF. The reaction mixture was brought to reflux temperature, held there for 30 min, and cooled to about 40 °C. There was added 0.55 mL H20 followed by 1.65 mL 10% aqueous NaOH and an additional 0.55 mL H20. The solids were removed by filtration and the filter cake washed with THF. The combined filtrate and washings were stripped of solvent under vacuum. The oily residue was crystallized from hexane to give 0.34 g (yield 71%) 5,6-dimethoxy-N-isopropyl-N-methyltryptamine, mp 71-73 °C. MS (in m/z) C5H12N+ 86 (100%) indolemethylene+ 190 (4%) parent ion 276 (9%). 

N,0-DMS NOR-5-MEO-DMT TRYPTAMINE, 5-METHOXY-N-METHYL INDOLE, 5-METHOXY-3-[2-(METHYLAMINO)ETHYL] SEROTONIN, N,O-DIMETHYL 5-METHOXY-N-METHYLTRYPTAMINE 5-METHOXY-3-[2-(METHYLAMINO)ETHYL]INDOLE N,0-DIMETHYLSEROTONIN... 

Serotonin, in an enzymatic interaction with the methyltetrahydrofolate one-carbon source, gives rise to the beta-carboline analogue, 6-HO-THbC. This happens also to be the plant alkaloid plectomine as well as a metabolite of THbC in the rat. Attempts to make DMT from methyltetrahydrofolate and N-methyltryptamine (NMT) gave rise exclusively to the carboline 2-Me-THbC. 

EXTENSIONS AND COMMENTARY N-Methyltryptamine (monomethyltryptamine, NMT) is an alkaloid that has been found in the bark, shoots and leaves of several species of Virola, Acacia and Mimosa. However, the major snuffs associated with these plant have been shown to also contain 5-MeO-DMT and are discussed there. NMT has been synthesized in a number of ways. One can react 3-(2-bromoethyl)indole with methylamine. NMT can be isolated as the benzoyl derivative from the methylation of tryptamine with methyl iodide followed by reaction with benzoyl chloride, with the hydrolysis of this amide with alcoholic KOH. It can also be synthesized from indole with oxalyl chloride, with the resulting glyoxyl chloride reacting with methylamine in ether to give indol-3-yl N-methylglyoxalylamide (mp 223-224 °C from IPA) which is obtained in a 68% yield, which is reduced to NMT to give the amine hydrochloride (mp 175-177 °C from ) in a 75% yield. The most simple and direct synthesis is the formamide reduction given above. 

Note Other methylated tryptamines with similar psychoactive properties include 6-fluoro-alpha-methyltrypta-5-methyltryptamine, N-methyltryptamine, 5-methyltryptamine. The dosage, effects, and contraindications are about the same for these as for the above. Some of the non-methylated derivatives are also active. These include 5-and 6-fluorotryptamine and 5- and 6-fluorotryptophan. 

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