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MS-245 potential nootropic?

Migrated topic.
This compound (2-[5-methoxy-1-(phenylsulfonyl)-1H-indol-3-yl]-N,N-dimethyltryptamine) MS-245 is essentially 5-methoxy-N,N-dimethyltryptamine with a phenylsulfonyl grouping off of the pyrrole ring's nitrogen.

MS-245 acts as a selective 5-HT6 receptor antagonist.

Other 5HT6 antagonists have shown to have nootropic properties, such as 5-methoxy-2-phenyl-N,N-dimethyltryptamine and 2-ethyl-5-methoxy-N,N-Dimethyltryptamine (EMDT)

I was interested in the potential of this novel tryptamine as a nootropic, but have found very little in terms of published research.



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downwardsfromzero said:
It looks much like an isostere of 5-MeO-2-Ph-DMT, and more easily approachable to boot.

It also posses very similar pharmocology to 5-methoxy-2-phenyl-N,N-dimethyltryptamine and 2-ethyl-5-methoxy-N,N-Dimethyltryptamine (EMDT)

This is actually turning out to be a rich field of study.

I'm just beginning to research these novel tryptamine compounds which interact with the serotonin 6 receptor, so I have a good deal of work to do, but as I learn and understand more I will continue to add to This thread

Below, in the sectioned off areas, some miscellaneous related research can be found:

Interaction of chiral MS-245 analogs at h5-HT6 receptors


5-HT(6) serotonin receptors are distributed within some dopamine terminal regions in the brain leading to suggestions that they might influence dopaminergic function. In the present study, the 5-HT(6) antagonist 5-methoxy-N,N-dimethyl-N(1)-benzenesulfonyltryptamine (MS-245) was without effect when administered (3.0-7.5 mg/kg) to rats trained to discriminate (+)amphetamine (1.0 mg/kg) from saline vehicle in a two-lever drug discrimination task. Administered in combination, 0.3 mg/kg (i.e., the ED(50) dose) of (+)amphetamine plus 5.0 mg/kg of MS-245 elicited 95% amphetamine-appropriate responding. Similar studies were conducted using rats trained to discriminate cocaine (8.0 mg/kg) from saline vehicle, but a combination of 2.0 mg/kg (i.e., the ED(50) dose) of cocaine together with relatively low doses of MS-245 resulted in the percent response (approximately 50%) expected from administration of this dose of cocaine or in disruption of the animals' behavior. The present results confirm findings from other laboratories that 5-HT(6) antagonists can modulate amphetamine-induced behavioral actions, and further extend these findings to an example of a different structural class of 5-HT(6) antagonists and to a different behavioral paradigm. Taken together, the data suggest that 5-HT(6) serotonin agents (or at least MS-245) could have potential clinical application in therapies that involve modulation of dopamine neurotransmission.


Binding of serotonin and N1-benzenesulfonyltryptamine-related analogs at human 5-HT6 serotonin receptors: receptor modeling studies.
A population of 100 graphics models of the human 5-HT6 serotonin receptor was constructed based on the structure of bovine rhodopsin. The endogenous tryptamine-based agonist serotonin (5-HT; 1) and the benzenesulfonyl-containing tryptamine-derived 5-HT6 receptor antagonist MS-245 (4a) were automatically docked with each of the 100 receptor models using a genetic algorithm approach. Similar studies were conducted with the more selective 5-HT6 receptor agonist EMDT (5) and optical isomers of EMDT-related analog 8, as well as with optical isomers of MS-245 (4a)-related and benzenesulfonyl-containing pyrrolidine 6 and aminotetralin 7. Although associated with the same general aromatic/hydrophobic binding cluster, 5-HT (1) and MS-245 (4a) were found to preferentially bind with distinct receptor conformations, and did so with different binding orientations (i.e., poses). A 5-HT pose/model was found to be common to EMDT (5) and its analogs, whereas that identified for MS-245 (4a) was found common to benzenesulfonyl-containing compounds. Specific amino acid residues were identified that can participate in binding, and evaluation of a sulfenamide analog of MS-245 indicates for the first time that the presence of the sulfonyl oxygen atoms enhances receptor affinity. The results indicate that the presence or absence of an N1-benzenesulfonyl group is a major determinant of the manner in which tryptamine-related agents bind at 5-HT6 serotonin receptors.


N-Benzenesulfonyl-5-methoxy-N,N-dimethyltryptamine (BS/5-OMe DMT; 5) was shown to bind at human 5-HT6 serotonin receptors with high affinity (Ki = 2.3 nM) relative to serotonin (Ki = 78 nM). Structural variation failed to result in significantly enhanced affinity. BS/5-OMe DMT acts as an antagonist of 5-HT-stimulated adenylate cyclase (pA2 = 8.88 nM) and may represent the first member of a novel class of 5-HT6 antagonists.


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