Analytical and behavioral characterization of N‐ethyl‐N‐isopropyllysergamide (EIPLA), an isomer of N⁶–ethylnorlysergic acid N,N‐diethylamide (ETH‐LAD)

Abstract

Preclinical investigations have shown that N‐ethyl‐N‐isopropyllysergamide (EIPLA) exhibits lysergic acid diethylamide (LSD)‐like properties, which suggests that it might show psychoactive effects in humans. EIPLA is also an isomer of N6‐ethylnorlysergic acid N,N‐diethylamide (ETH‐LAD), a lysergamide known to produce psychedelic effects in humans that emerged as a research chemical. EIPLA was subjected to analysis by various forms of mass spectrometry, chromatography (GC, LC), nuclear magnetic resonance (NMR) spectroscopy, and GC condensed‐phase infrared spectroscopy. The most straightforward differentiation between EIPLA and ETH‐LAD included the evaluation of mass spectral features that reflected the structural differences (EIPLA: N6‐methyl and N‐ethyl‐N‐isopropylamide group; ETH‐LAD: N6‐ethyl and N,N‐diethylamide group). Proton NMR analysis of blotter extracts suggested that EIPLA was detected as the base instead of a salt, and two blotter extracts suspected to contain EIPLA revealed the detection of 96.9 ± 0.5 μg (RSD: 0.6%) and 85.8 ± 2.8 μg base equivalents based on LC–MS analysis. The in vivo activity of EIPLA was evaluated using the mouse head‐twitch response (HTR) assay. Similar to LSD and other serotonergic psychedelics, EIPLA induced the HTR (ED50 = 234.6 nmol/kg), which was about half the potency of LSD (ED50 = 132.8 nmol/kg). These findings are consistent with the results of previous studies demonstrating that EIPLA can mimic the effects of known psychedelic drugs in rodent behavioral models. The dissemination of analytical data for EIPLA was deemed justifiable to aid future forensic and clinical investigations.

Structural analysis of an lysergic acid diethylamide (LSD) analogue N‐methyl‐N‐isopropyllysergamide (MiPLA): Insights from Rotamers in NMR spectra

“…Similar NMR spectral patterns have been reported for MiPLA 13 and EiPLA. 19 HSQC spectra associated individual 13 C signals with corresponding 1 H partners (not only C23, C22, C21, and C8, but also C17, C8, and C5), which were also revealed to be rotamer pairs (Figures S35 and S36). Because these carbon atoms are located close to the amide group, it was considered that their 13 C signals may be affected by rotational isomerism.…”

“…10 However, some compounds are still psychoactive. 11 Owing to the presence of LSD derivatives in sheet-type drug products (also known as blotter papers) [12][13][14][15][16][17][18][19][20] it is important to obtain pure standard materials and develop suitable analytical conditions for the rapid regulation of these compounds. Hence, this study focused on N-methyl-N-isopropyl substituted LSD derivative, namely [(6aR,9R)-N-isopropyl-N,7-dimethyl-4,6,6a,7,8,9-hexahydroindolo [4,3-fg]quinoline-9-carboxamide], or MiPLA (Figure 1).…”