Volume 10, Issue 2 p. 310-322
RESEARCH ARTICLE

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

Simon D. Brandt

Simon D. Brandt

School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK

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Pierce V. Kavanagh

Pierce V. Kavanagh

Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, Dublin 8, Ireland

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Brendan Twamley

Brendan Twamley

School of Chemistry, Trinity College Dublin, Dublin 2, Ireland

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Folker Westphal

Folker Westphal

Section Narcotics/Toxicology, State Bureau of Criminal Investigation Schleswig-Holstein, Kiel, Germany

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Simon P. Elliott

Simon P. Elliott

Alere Forensics, Malvern Hills Science Park, Malvern, UK

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Jason Wallach

Jason Wallach

Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, Pennsylvania, USA

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Alexander Stratford

Alexander Stratford

Synex Synthetics BV, Delft, The Netherlands

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Landon M. Klein

Landon M. Klein

Department of Neurosciences, University of California San Diego, La Jolla, California, USA

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John D. McCorvy

John D. McCorvy

Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA

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David E. Nichols

David E. Nichols

Division of Chemical Biology and Medicinal Chemistry, University of North Carolina, Chapel Hill, North Carolina, USA

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Adam L. Halberstadt

Corresponding Author

Adam L. Halberstadt

Department of Psychiatry, University of California San Diego, La Jolla, California, USA

Correspondence

Adam L. Halberstadt, Department of Psychiatry, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0804 USA.

Email: [email protected]

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First published: 05 June 2017
Citations: 40

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-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.