So, here's something that might stimulate some interesting thoughts....
Apparently this study just came out last month:
Receptor binding profiles and quantitative structure-affinity relationships of some 5-substituted-N,N-diallyltryptamines.
I'm looking at the PDF right now. It's your typical modern receptor binding study with a huge PDSP screening, and it focuses on DALT, 5-MeO-DALT, and the interesting but mostly novel 5-F-DALT, 5-Cl-DALT, 5-Br-DALT, and 5-Me-DALT. I've posted the data chart below, which is given in the PDF.
Key: (
1) DALT, (
2) 5-F-DALT, (
3) 5-Cl-DALT, (
4) 5-Br-DALT, (
5) 5-Me-DALT, (
6) 5-MeO-DALT
The study claims: "The DALT compounds were initially screened at 45 different receptors and transporters. From this set, 27 sites met the 10 μM threshold criterion for secondary analysis and
Ki determination. Notably, none of the following sites met the 10 μM criterion: beta adrenergic (β
1-β
3); dopaminergic D
1, D
4, D
5; GABAergic (flunitrazepam GABA
A, muscimol GABA
A, and peripheral benzodiazepine sites); muscarinic (M
1-M
5); 5-HT
3; δ-opioid; histaminergic H
2 and H
4 receptors.
All of the test compounds exhibited Ki values of less than 10 μM at the following sites: serotonergic receptors 5-HT
1A, 5-HT
1D, 5-HT
1E, 5-HT
2A, 5-HT
2B, 5-HT
2C, and 5-HT
6; adrenergic receptors α
2A, α
2B, and α
2C; histamine receptor H
1;
κ opioid receptor (κOR); sigma receptors σ
1 and σ
2; DAT and SERT monoamine reuptake transporters."
I have bolded my favorite part.
Yes, DALT, 5-MeO-DALT, and the rest of these compounds all have less than 10,000 nM affinity for kappa-opioid receptors. (And, for those with particularly novel interests, 5-Cl-DALT and 5-Br-DALT both have some affinity for mu-opioid receptors!) This is particularly interesting to me because I am aware of one other study which claims, using to my knowledge unpublished information, that DPT has some relevant affinity for kappa-opioid receptors as well. Notably, the same group which does the binding studies (the PDSP) also found DPT to have an affinity of 2,579 nM at 5-HT2A, similar to 2,323 nM for DMT, so I think it's worth considering that an affinity of less than 10,000 nM at another site could translate into
very relevant activity among these compounds.
This is a really intriguing finding to me. I really wish they had thought to include 4-HO-DALT or 4-AcO-DALT in their testing, or maybe even 4-MeO-DALT as they also suggested that increasing the bulk of 5-substitution should increase kappa-opioid receptor affinity, but it is what it is. I have to say though that when I have taken 4-AcO-DALT, particularly when I took 60 mg orally, I
really felt like there was a salvia-like dissociation going on, and I even had an indistinguishable "spinning gravity" effect to my movement. I had convinced myself that maybe it was something related to dopamine receptor stimulation at the time, but perhaps there could be more to it than that? I have also felt this effect to a similar extent with both 4-HO-MPT and 4-HO-DET, and I really wanted to characterize those as salvia-like at the time too, but I keep pushing that logic off... but maybe there's no need to.
Anyway, does anyone else find this is as potentially interesting as I do?
