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Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM-775)

Brandt, SD and Kavanagh, PV and Twamley, B and Westphal, F and Elliott, SP and Wallach, J and Stratford, A and Klein, LM and McCorvy, JD and Nichols, DE and Halberstadt, AL (2017) Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM-775). Drug Testing and Analysis. ISSN 1942-7611

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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 stereoscopy (NMR), gas chromatography mass spectrometry (GC-MS), high mass accuracy electrospray MS/MS, 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-HT1A and 5-HT2A receptors. Head twitch studies were conducted in C57BL/6J mice to determine whether LSM-775 activates 5-HT2A receptors and produces hallucinogen-like effects in vivo. LSM-775 did not induce the head twitch response unless 5-HT1A receptors were blocked by pretreatment with the antagonist WAY-100,635 (1 mg/kg, subcutaneous). These findings suggest that 5-HT1A 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.

Item Type: Article
Additional Information: This is the accepted version of the following article: Brandt SD, Kavanagh PV, Twamley B, et al. Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM-775). Drug Test Anal. 2017. https://doi.org/10.1002/dta.2222, which has been published in final form at http://dx.doi.org/10.1002/dta.2222
Uncontrolled Keywords: 0301 Analytical Chemistry, 1115 Pharmacology And Pharmaceutical Sciences
Subjects: Q Science > QD Chemistry
R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Wiley
Date Deposited: 05 Jun 2017 09:15
Last Modified: 12 Jul 2017 10:04
DOI or Identification number: 10.1002/dta.2222
URI: http://researchonline.ljmu.ac.uk/id/eprint/6616

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