Tryptamines potency

Fluoro-a-methyltryptamine is another tryptamine that can be ordered from Aldrich and many other chemical suppliers. This drug does not require a statement, as described above, and its effects are very pleasant (much like psilocyn). Also, it can be eaten instead of smoked or snorted. The major drawback here is the 100 a gram price combined with the higher 25 mg oral dose. Smoking or snorting may increase the potency. 

Back to the metabolism discussion. And to the search for the actual drug, the magic bullet, that actually precipitated a model schizophrenic state. If one were to find it, one could look skillfully for the counterpart in the human animal, the one that simply appeared on the scene from some mismanaged metabolic process, and thus could be blamed for mental illness. It had been observed that the longer the chains on the N,N-disubstituted tryptamine, the less the potency. And the longer the chains, the less of the drug was excreted as the 6-hydroxyl metabolite. This focused attention on the hydroxy metabolites of the two simplest and most potent of the dialkyltryptamines, DMT and DET. 

There is the raw stuff potentially available to answer this question. There are a couple of compounds known with the sulfur in the 4-position, which is the location of the oxygen atom in psilocybin. The 4-thio analogues have been synthesized from 4-methylihio-indole, via the oxalyl chloride method and reaction with the appropriate amine. With dimethylamine, the indoleglyoxylamide was made in a43% yield and had amp 163-164 °C. With diisopropylamine, the amide was made in a 27% yield and had a mp 190-192 °C. The final amines were prepared by the reduc tion of these amides with L AH in THF. N,N-Dimethyl-4-thio tryptamine (4-MeS-DMT) was obtained in a 68% yield and melted at 108-110 °C N,N-diisopropyl-4-methylthiotryptamine (4-MeS-DIPT) was obtained in a 61% yield and melted at 92-94 °C. In animal studies of behavioral disruption with these three compounds, there was systematic drop of potency in going from the 5-MeS-DMT to 4-MeS-DMT to 4-MeS-DIPT. 

The oral activity of tryptamines that are degraded by MAO can be enhanced by chemicals called monoamine oxidase inhibitors (MAOI). This synergism serves as the basis for the Amazonian entheogenic brew, ayahuasca (which means vine of the souls ), where DMT is rendered orally active by the presence of MAOI harmala alkaloids from the plant Banisteriopsis caapi (Metzner 1999). Anoliher botanical source of the MAOI harmala alkaloids harmaline and harmine is the seed of the Syrian rue, Beganum harmala, a bush related to the creosote, native to Asia and Africa. There are anecdotal reports that the potency of psilocybin... 

Not only the real nature of the specific mesencephalic enhancer receptors but also the endogenous ligands to these receptors remain unresolved. The high potency of (-)-BPAP in comparison to the already identified natural enhancer substances, PEA and tryptamine, is remarkable. This difference gives justification for the search for much more potent natural enhancer substances than PEA and tryptamine. 

Evidence in favour of this concept could be provided by a comparison of enantiomeric potency ratios. If there was good agreement between the potency ratios of, for example (+)- and (—)-LSD, (+)- and (—)-a-methyl-tryptamine and (+)- and (—)-amphetamine, and if the fundamental molecular geometry of the (+ )-isomers was similar, the contention that these drugs act by a similar mechanism would be strengthened. 

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