Methoxy-methyltryptamine

Serotonin, A-methylserotonin, bufotenine, and 5-methoxy-A-methyltryptamine become readily available in a simple way by applying nucleophilic substitution reactions in 1-hydroxytryptamine chemistry (99H1157, 2001CPB87). 

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. 

Banisteriopsis caapi The primary hallucinogenic constituents of B. caapi are the jS-carbolines. These include harmaline, tetrahydroharmine, harmol, harmic acid methyl ester, harmic amide, acetyl norharmine, harmine A/-oxide, harmalinic acid, and ketotetrahydronorharmine (figure 9.8). B. rusbyana also contains DMT, as well as A/-methyltryptamine, 5-methoxy-N,/V-dimethyltryptamine, and 5-hydroxy-N,/V-dimethyltryptamine (bufotenin). /V-methyltetrahydro-jS-carboline is found in trace amounts. 

MEO-a-MT TRYPTAMINE, 5-METHOXY-a-METHYL INDOLE, 3-(2-AMINOPROPYL)-5-METHOXY SEROTONIN, a,O-DIMETHYL 5-METHOXY-a-METHYLTRYPTAMINE 3-(2-AMIN0PR0PYL)-5-METH0XYIND0LE a,0-DIMETHYLSER0T0NIN ALPHA-0... 

TRYPTAMINE, N-ISOPROPYL-4-METHOXY-N-METHYL INDOLE, 3-[2-(ISOPROPYLMETHYLAMINO)ETHYL]-4-METHOXY N-ISOPROPYL-4-METHOXY-N-METHYLTRYPTAMINE 3-[2-(ISOPROPYLMETHYLAMINO)ETHYL]-4-METHOXYINDOLE... 

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-... 

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... 

Christian et al. refers to Dr. Samuel Christian and his associates at the University of Alabama in Birmingham s Neurosciences Program in 1975 they identified DMT, 5-methoxy-DMT, 5-methoxy-N,N-DMT, N-methyltryptamine and tryptamine in human cerebrospinal fluid. In May 1977, Dr. Wolfgang Vogel of the Jefferson Medical College in Philadelphia isolated 5-methoxy-DMT in brain tissue the Christian team also found DMT there. 

A report that sheep fed on a perennial grass, Phalaris tuberosa L., developed a condition known as staggers led to the investigation of a related species, P. arundinacea L., and the subsequent isolation from it of 5-methoxy-A-methyltryptamine (XVIII R = H) (116). 5-Methoxy-iV.A-dimethyltryptamine (XVIII R = Me) also occurs naturally, and has been isolated from Dictyoloma incane-scens DC. (40). Both bases have recently been shown to be present in the bark of Piptadenia peregrina Benth. (73a). 

Methoxy-N,N-d1methyltryptamine 2-Methyl-1,2,3,4-tetrahydro-B-carboline 5-Methoxy-N-methyltryptamine 2-Methyl -6-methoxy-l,2,3,4,-tetrahydro-B-carboline... 

The diazoketone 724, prepared from 6-methoxy-l-methyltryptamine in an unexceptional manner, was treated with trifluoroacetic acid to give the vinylogous amide 725 in 35% yield as a mixture of epimers. Treatment of the mixture with lithium in liquid NH3 gave 525 in 92% yield. 

Methoxy-N-methyltryptamine from reed canary grass (Wilkinson 1958). Tryptamine from Petahstyfis fabicheoides (Johns 1966)... 

Wilkinson, S. S-Methoxy-N-methyltryptamine A New Indole Alkaloid from Phaiaris arundianacea L. ... 

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