4-Desmethylene-LSD
4-Desmethylene-LSD, also known as 4-nor-LSD, 3,5-seco-LSD, or DEIMDHPCA, is an indole derivative and a "partial" or simplified lysergamide which is closely related to the highly potent serotonergic psychedelic lysergic acid diethylamide. It is specifically the analogue of LSD in which one of LSD's carbon atoms in the ergoline ring system, the carbon at position 4, has been removed. This in turn renders the molecule more flexible and makes it a partially conformationally constrained indolic phenethylamine-containing compound rather than an ergoline. 4-Desmethylene-LSD is known to be a highly potent serotonin 5-HT2 receptor agonist similarly to LSD and to produce psychoplastogenic effects.
Pharmacology
Like LSD, the drug is known to be a highly potent serotonin 5-HT2A and 5-HT2C receptor agonist in vitro. Its affinities are in the ranges of 10–100nM for the serotonin 5-HT2A receptor and 100–1,000nM for the serotonin 5-HT2C receptor, while its activational potencies are less than 10nM for the serotonin 5-HT2A receptor and in the range of 10–100nM for the serotonin 5-HT2C receptor. 4-Desmethylene-LSD was the most potent serotonin 5-HT2A receptor agonist of 27evaluated ergoline-like compounds. In line with its serotonin 5-HT2A receptor agonism, and similarly to LSD and other psychedelics, 4-desmethylene-LSD has been found to produce psychoplastogenic effects on neurite growth in vitro.Many serotonin 5-HT2A receptor agonists, for instance LSD, produce psychedelic effects in humans. The publication that reported 4-desmethylene-LSD specifically pertained to psychoplastogenic ergoline-like compounds with no or reduced hallucinogenic activity for potential therapeutic use. However, the hallucinogenic-related properties of 4-desmethylene-LSD and the other reported compounds, for instance their effects in the head-twitch response assay, were not individually described. As such, it remains unclear whether or not 4-desmethylene-LSD could have psychedelic effects in humans.
History
4-Desmethylene-LSD was first described in the literature by 2021. It has been patented by Delix Therapeutics.Related compounds
Other related compounds in which one or more other carbons have been removed from the LSD's ergoline ring system to produce simplified and less-rigid phenethylamines and tryptamines include N-DEAOP-NMT and NDTDI. Desvinyl-LSD is the analogue of LSD in which the carbon atoms at positions 9 and 10 of the ergoline ring system have been removed to make a fully non-rigid tryptamine, while 9-desmethine is the analogue of LSD in which the methine at position 9 has been removed to make a rigid tricyclic tryptamine. Desvinyl-LSD has been found to produce LSD-like effects in rodents, while 9-desmethine-LSD has been encountered as a novel recreational and designer drug and made illegal in parts of Europe.File:LSD, 4-desmethine-LSD, and desvinyl-LSD.png|thumb|upright=2|right|450px|class=skin-invert-image|Structures of LSD, NDTDI , and N-DEAOP-NMT .
The analogue of 4-desmethylene-LSD without the ethyl groups on the amide has been described. In addition, 4-desmethylene-LSD's analogue without the amide ethyl groups and with a phenyl ring instead of the indole ring has been described. Their activities were not reported.
WXVL_BT0793LQ2118, an analogue of 4-desmethylene-LSD lacking the N,''N-diethyl-carboxamide moiety and with a fluorine at the 6-position, has been reported. It was identified via in silico'' screening of 1.6billion molecules for serotonin 5-HT2A receptor agonism with AlphaFold2. Following identification, the drug was assessed and found to be a potent serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonist.