Description
Why DM-506 as a non-hallucinogenic psychedelic
- In summary, the most potent non-hallucinogenic psychedelics in order is: DM-506 > Ibogainalog ∼ Noribogainalog > Catharanthalog > Zalsupindole > Tabernanthalog
- DM-506 lacks any HTR (head-twitch response) which is a unique response to hallucinogenic psychedelics like TCB-2 and DOI in mice; making DM-506 a non-hallucinogenic psychedelic [x]
- DM-506 is a significantly more potent 5-HT2A agonist (EC50 = 34 nM)Â than Ibogainalog (EC50 = 85 nM) and Tabernanthalog (EC50 = 1121 nM), making DM-506 >30x more potent than Tabernanthalog [x]
- DM-506 has >9x selectivity for 5-HT2A (Ki = 19 nM) over the undesirable 5-HT2C (Ki = 176 nM), while Ibogainalog and Tabernanthalog have much lower selectivity [x]
- DM-506 has significantly higher blood brain barrier permeability (LogBBB = 0.76) than Tabernanthalog (LogBBB = 0.65) and Ibogainalog (LogBBB = 0.62) [x]. Thus, DM-506 likely has higher neuronal permeability than Ibogainalog and Tabernanthalog by not having the added bulk of a Methoxy (MeO) or Hydroxy (HO) group. This is seen with DMT being more neuronally permeable than 5-MeO-DMT and Psilocin (4-HO-DMT), allowing greater intracellular 5-HT2A interaction [x]
- DM-506 is a very strong inhibitor of 5-HT7’s response (-52.3%) compared to Ibogainalog (-35.9%) and Tabernanthalog (-14.3%), about as strong as SB-269970 which is one of the most potent 5-HT7 antagonist/inverse agonists known [x]
- Interestingly, DM-506 has a higher 5-HT2A affinity (Ki = 19 nM) than DMT (Ki = 127.0 nM) and Psilocin (Ki = 107.2 nM) [x, x]
Why DM-506 over the isoDMT derivative RC candidates
- In summary, both the parent compound, isoDMT, and its derivatives have far too weak 5-HT2A affinity to be chosen over the non-hallucinogenic Ibogaine derivatives
- Though the isoDMT derivatives are interesting non-hallucinogenic psychedelics, with Zalsupindole being the only active one without a MAOI, isoDMT has a low 5-HT2A affinity (Ki = 600 nM) [x]
- There’s no available data on Zalsupindole‘s 5-HT2A affinity, it’s hard to believe it’s much better considering that 6-MeO-isoDMT, which is structurally the closest to Zalsupindole, has an even lower 5-HT2A affinity (Ki = 1 040 nM) [x, x]
- Therefore, Zalsupindole (AAZ-A-154) is a close analogue of 6-MeO-isoDMTÂ which has low affinity, making it far less potent than DM-506
