Return of the lysergamides. Part II: Analytical and behavioural characterization of N6-allyl-6-norlysergic acid diethylamide (AL-LAD) and (2'S,4'S)-lysergic acid 2,4-dimethylazetidide (LSZ).
Lysergic acid N,N-diethylamide (LSD) is perhaps one of the most intriguing psychoactive substances known and numerous analogs have been explored to varying extents in previous decades. In 2013, N6-allyl-6-norlysergic acid diethylamide (AL-LAD) and (2'S,4'S)-lysergic acid 2,4-dimethylazetidide (LSZ) appeared on the 'research chemicals'/new psychoactive substances (NPS) market in both powdered and blotter form. This study reports the analytical characterization of powdered AL-LAD and LSZ tartrate samples and their semi-quantitative determination on blotter paper. Included in this study was the use of nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), low and high mass accuracy electrospray MS(/MS), high performance liquid chromatography diode array detection and GC solid-state infrared analysis. One feature shared by serotonergic psychedelics, such as LSD, is the ability to mediate behavioural responses via activation of 5-HT2Areceptors. Both AL-LAD and LSZ displayed LSD-like responses in male C57BL/6 J mice when employing the head-twitch response (HTR) assay. AL-LAD and LSZ produced nearly identical inverted-U-shaped dose-dependent effects, with the maximal responses occurring at 200 µg/kg. Analysis of the dose responses by nonlinear regression confirmed that LSZ (ED50= 114.2 nmol/kg) was equipotent to LSD (ED50= 132.8 nmol/kg) in mice, whereas AL-LAD was slightly less potent (ED50= 174.9 nmol/kg). The extent to which a comparison in potency can be translated directly to humans requires further investigation. Chemical and pharmacological data obtained from NPS may assist research communities that are interested in various aspects related to substance use and forensic identification. Copyright © 2016 John Wiley & Sons, Ltd.
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
Simon D
SD
Brandt
Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. James Hospital, Dublin 8, Ireland.
Pierce V
PV
Kavanagh
State Bureau of Criminal Investigation Schleswig-Holstein, Section Narcotics/Toxicology, Mühlenweg 166, D-24116, Kiel, Germany.
Folker
F
Westphal
ROAR Forensics, Malvern Hills Science Park, Geraldine Road, WR14 3SZ, UK.
Simon P
SP
Elliott
Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, 19104, USA.
Jason
J
Wallach
Department of Chemistry and Biochemistry, University of the Sciences, 600 South 43rd Street, Philadelphia, PA, 19104, USA.
Tristan
T
Colestock
Department of Chemistry, University of Toronto, St. George Street, Toronto, ON, M5S 3H6, Canada.
Timothy E
TE
Burrow
Isomer Design, 4103-210 Victoria Street, Toronto, ON, M5B 2R3, Canada.
Stephen J
SJ
Chapman
Synex Ltd, 67-68 Hatton Garden, N13 4BS, London, UK.
Alexander
A
Stratford
Division of Chemical Biology and Medicinal Chemistry, University of North Carolina, Genetic Medicine Building 120 Mason Farm Road, Chapel Hill, NC, 27599, USA.
David E
DE
Nichols
Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0804, USA.
Adam L
AL
Halberstadt
D000818:Animals; D006801:Humans; D008238:Lysergic Acid Diethylamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*
D011619:Psychotropic Drugs; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D008238:Lysergic Acid Diethylamide
5-HT2A receptors; LSD; lysergamides; new psychoactive substances; psychedelics