N&PD Moderators: Skorpio | thegreenhand
Something thats feasable to stick on that 4 position of DMT, to make it orally active, not get eaten by MAO so fast, "somewhat" legal, and hoping that altering the molecule over on that side and not the DMT side would retain the "DMT goodness" would be really nice to discover...
5-HT2A receptor binding data
The simple parent compounds tryptamine (5), NMT (212), and DMT (45) displayed low affinities
between 1 μM and 2 μM for the ketanserin (48) labeled 5-HT2A receptor. By 5-methoxy
lation affinity could be increased to 150 nM for 5-MeO-tryptamine (358) and to about 550 nM
for 5-MeO-NMT (208) and 5-MeO-DMT (15). 5-HT (6) itself had an affinity of 140 nM, comparable
to that of 5-MeO-tryptamine (358).
The tested N-benzylated NMT derivatives 210 and 207 exhibited affinities between 800 nM
and 900 nM, independent of 5-methoxylation. 5-MeO-N-(4-Br-benzyl)-tryptamine (19) had an
affinity of only 530 nM, not different to that of 5-MeO-NMT (208) and only 1/4 that of 5-HT (6)
and the N-unsubstituted 5-MeO-tryptamine (358). This result will be discussed in detail
below.
Binding affinities at the 5-HT1A compared to the 5-HT2A receptor
Not a single compound from this project showed more than a five-fold selectivity for the
5-HT2A over the 5-HT1A receptor, while a few compounds with greater than 50-fold selectivity
for the 5-HT1A over the 5-HT2A receptor could be identified. The latter are the simple tryptamines
5-MeO-tryptamine (358) (95-fold), 5-MeO-NMT (208) (275-fold), and 5-MeO-DMT
(15) (134-fold), the alkyl substituted ligands n-butyl-5-MeO-NMT (332) (72-fold), n-pentyl-
5-MeO-NMT (338) (69-fold), n-octyl-5-MeO-NMT (344) (479-fold), cyclopentylmethyl-5-MeONMT
(216) (62-fold), cyclohexylmethyl-5-MeO-NMT (218) (65-fold), isobutyl-5-MeO-NMT
(310) (96-fold), allyl-5-MeO-NMT (306) (108-fold), cyclohexylpropyl-5-MeO-NMT (314)
(177-fold), and cyanoethyl-5-MeO-NMT (294) (43-fold), as well as the aromatic ring