Drug Testing and Analysis
June 5, 2017
Simon D. Brandt, Pierce V. Kavanagh, Brendan Twamley et al.
56 citations
Lysergic acid morpholide (LSM-775), a structural relative of LSD, appeared on the market for new psychoactive substances in 2013, but its potency and psychoactive effects in humans have been disputed. This investigation characterized a powdered sample using multiple analytical techniques and tested its receptor activity. LSM-775 acted as a nonselective agonist at 5-HT1A and 5-HT2A receptors. In head twitch studies with C57BL/6J mice, LSM-775 did not induce the head twitch response unless 5-HT1A receptors were blocked by the antagonist WAY-100,635 (1 mg/kg, subcutaneous). The findings suggest that activation of 5-HT1A receptors by LSM-775 masks its hallucinogen-like effects, consistent with reports that it produces only weak LSD-like effects in humans.
Psychopharmacology
February 14, 2019
Adam L. Halberstadt, Landon M. Klein, Muhammad Chatha et al.
25 citations
The lysergamide ECPLA, a close structural analog of LSD, binds with high affinity to serotonin, adrenergic, and dopamine receptors, and acts as a potent agonist at the 5-HT₂A receptor, which mediates psychedelic effects. In mice, ECPLA induced head twitches with an ED₅₀ of 317.2 nmol/kg, about 40% as potent as LSD. Two other analogs, LAMPA (ED₅₀ = 358.3 nmol/kg) and MIPLA (ED₅₀ = 421.7 nmol/kg), showed similar or slightly lower potency. These findings indicate that ECPLA, MIPLA, and LAMPA share pharmacological properties with LSD and other lysergamide hallucinogens.
UNC Libraries
October 29, 2020
Simon D. Brandt, Maria F. Sassano, David E. Nichols et al.
4 citations
A series of N-benzylated-5-methoxytryptamine analogues and N-benzylated analogues of 2,5-dimethoxy-4-iodophenethylamine (2C-I) were synthesized and tested. Most compounds showed highest affinity for the 5-HT2 family of serotonin receptors. Substitution at the para position of the benzyl group reduced affinity, while ortho or meta substitution enhanced it. Large lipophilic groups improved affinity but often reduced functional activity. Functional potency was measured at human 5-HT2A, 5-HT2B, and 5-HT2C receptors and rat 5-HT2A and 5-HT2C receptors using intracellular calcium mobilization. Several tryptamine congeners were very potent functionally (EC50 values from 7.6 to 63 nM) but were mostly partial agonists. In mouse head twitch tests, many compounds induced the behavior, which correlated significantly with functional potency at the rat 5-HT2A receptor.