Lysergamides of Isomeric 2,4-Dimethylazetidines Map the Binding Orientation of the Diethylamide Moiety in the Potent Hallucinogenic Agent N,N-Diethyllysergamide (LSD)
J. Med. Chem., 45 (19), 4344-4349 (2002)
Lysergic acid amides were prepared from (R,R)-(-)-, (S,S)-(+)-, and cis-2,4-dimethyl azetidine. The dimethylazetidine moiety is considered here to be a rigid analogue of diethylamine, and thus, the target compounds are all conformationally constrained analogues of the potent hallucinogenic agent, N,N-diethyllysergamide, LSD-25.
Pharmacological evaluation showed that (S,S)-(+)-2,4-dimethylazetidine gave a lysergamide with the highest LSD-like behavioral activity in the rat two lever drug discrimination model that was slightly more potent than LSD itself. This same diastereomer also had the highest affinity and functional potency at the rat serotonin 5-HT2A receptor, the presumed target for hallucinogenic agents, and a receptor affinity profile in a panel of screens that was most similar to that of LSD itself.
Both cis- and the (R,R)-trans-dimethylazetidines gave lysergamides that were less potent in all relevant assays.....
I guess it’s conceivable that others could have discovered these compounds before Nichols group, as well as other newer analogues thought to have activity, but I think it would be improbable, as the chemistry gets pretty serious and requires state of the art equipment and expensive chemicals.
The only real way of finding out if other compounds are common in blotters, liquid etc would be to analyze the LSD in question. Looking at lab reports for past police LSD seizures may help.
If I again get the chance to talk to the chief of forensics drug research I met recently, I’ll put this question to him.
Plague Bearer, your question of possible interactions with side reaction or break down impurities is interesting. Synergy or potentiation can often be complicated to predict, particularly when concerning the incredibly complex pharmacophore of LSD at receptors. LSD and some (non-breakdown) analogues are known to be agonists also at 5HT1a receptors, resulting in short period increases in serotonin levels.
With the nature of LSD, I think it would be difficult at the least to achieve repeatable results of test using LSD + specific impurities. Human tests would probably be prohibited anyway, and mice just can’t quite explain well enough. Perhaps as Rhodium suggested, the mice could tap out Morse code on their little beeping delivery levers