Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM‐775)
Simon D. Brandt, Pierce V. Kavanagh, Brendan Twamley, Folker Westphal, Simon Elliott, Jason Wallach, Alexander Stratford, Landon M. Klein, John D. Mccorvy, David E. Nichols, Adam L. Halberstadt
Drug Testing and Analysis June 5, 2017 DOI: 10.1002/dta.2222 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | C57BL/6J mice |
| Intervention | 635 |
| Dose | 1 mg/kg (WAY-100,635) |
| Measures | head twitch response |
| Topics | LSD Serotonin |
| Keywords | Hallucinogen High-performance liquid chromatography Receptor Partial agonist Pharmacology Stereochemistry Biochemistry |
| Citations | 56 |
| Key findings | LSM-775 did not induce the head twitch response in mice unless 5-HT1A receptors were blocked, suggesting its 5-HT1A activation masks hallucinogen-like effects. |
Abstract
Lysergic acid diethylamide (LSD) is perhaps one of the best‐known psychoactive substances and many structural modifications of this prototypical lysergamide have been investigated. Several lysergamides were recently encountered as ‘research chemicals’ or new psychoactive substances (NPS). Although lysergic acid morpholide (LSM‐775) appeared on the NPS market in 2013, there is disagreement in the literature regarding the potency and psychoactive properties of LSM‐775 in humans. The present investigation attempts to address the gap of information that exists regarding the analytical profile and pharmacological effects of LSM‐775. A powdered sample of LSM‐775 was characterized by X‐ray crystallography, nuclear magnetic resonance spectroscopy (NMR), gas chromatography mass spectrometry (GC–MS), high mass accuracy electrospray MS/MS, high performance liquid chromatography (HPLC) diode array detection, HPLC quadrupole MS, and GC solid‐state infrared analysis. Screening for receptor affinity and functional efficacy revealed that LSM‐775 acts as a nonselective agonist at 5‐HT 1A and 5‐HT 2A receptors. Head twitch studies were conducted in C57BL/6J mice to determine whether LSM‐775 activates 5‐HT 2A receptors and produces hallucinogen‐like effects in vivo . LSM‐775 did not induce the head twitch response unless 5‐HT 1A receptors were blocked by pretreatment with the antagonist WAY‐100,635 (1 mg/kg, subcutaneous). These findings suggest that 5‐HT 1A activation by LSM‐775 masks its ability to induce the head twitch response, which is potentially consistent with reports in the literature indicating that LSM‐775 is only capable of producing weak LSD‐like effects in humans.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 43
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- Designer drugs: mechanism of action and adverse effects Archives of Toxicology April 1, 2020
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- Structure–Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice ACS Pharmacology & Translational Science November 2, 2022
- Return of the lysergamides. Part V: Analytical and behavioural characterization of 1‐butanoyl‐d‐lysergic acid diethylamide (1B‐LSD) Drug Testing and Analysis May 13, 2019
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Cites 29
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- Do functional relationships exist between 5-HT1A and 5-HT2 receptors? Pharmacology, Biochemistry, and Behavior August 1, 1990
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