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1.
Drug Test Anal ; 14(8): 1503-1518, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35524430

ABSTRACT

Lysergic acid diethylamide (LSD) is known to induce powerful psychoactive effects in humans, which cemented its status as an important tool for clinical research. A range of analogues and derivatives has been investigated over the years, including those classified as new psychoactive substances. This study presents the characterization of the novel lysergamide N,N-diethyl-1-propanoyl-6-(prop-2-en-1-yl)-9,10-didehydroergoline-8ß-carboxamide (1P-AL-LAD) using various mass spectrometric, gas- and liquid chromatographic and spectroscopic methods. In vitro metabolism studies using pooled human liver microsomes (pHLM) confirmed that 1P-AL-LAD converted to AL-LAD as the most abundant metabolite consistent with the hypothesis that 1P-AL-LAD may act as a prodrug. Fourteen metabolites were detected in total; metabolic reactions included hydroxylation of the core lysergamide ring structure or the N6 -allyl group, formation of dihydrodiol metabolites, N-dealkylation, N1 -deacylation, dehydrogenation, and combinations thereof. The in vivo behavioral activity of 1P-AL-LAD was evaluated using the mouse head twitch response (HTR), a 5-HT2A -mediated head movement that serves as a behavioral proxy in rodents for human hallucinogenic effects. 1P-AL-LAD induced a dose-dependent increase in HTR counts with an inverted U-shaped dose-response function, similar to lysergic acid diethylamide (LSD), psilocybin, and other psychedelics. Following intraperitoneal injection, the median effective dose (ED50 ) for 1P-AL-LAD was 491 nmol/kg, making it almost three times less potent than AL-LAD (174.9 nmol/kg). Previous studies have shown that N1 -substitution disrupts the ability of lysergamides to activate the 5-HT2A receptor; based on the in vitro metabolism data, 1P-AL-LAD may induce the HTR because it acts as a prodrug and is metabolized to AL-LAD after administration to mice.


Subject(s)
Hallucinogens , Prodrugs , Animals , Chromatography, Liquid/methods , Hallucinogens/chemistry , Hallucinogens/pharmacology , Humans , Lysergic Acid Diethylamide/analogs & derivatives , Mice
2.
BMC Res Notes ; 15(1): 183, 2022 May 18.
Article in English | MEDLINE | ID: mdl-35585609

ABSTRACT

OBJECTIVE: The fungus Metarhizium brunneum produces ergot alkaloids of the lysergic acid amide class, most abundantly lysergic acid α-hydroxyethylamide (LAH). Genes for making ergot alkaloids are clustered in the genomes of producers. Gene clusters of LAH-producing fungi contain an α/ß hydrolase fold protein-encoding gene named easP whose presence correlates with LAH production but whose contribution to LAH synthesis in unknown. We tested whether EasP contributes to LAH accumulation through gene knockout studies. RESULTS: We knocked out easP in M. brunneum via a CRISPR/Cas9-based approach, and accumulation of LAH was reduced to less than half the amount observed in the wild type. Because LAH accumulation was reduced and not eliminated, we identified and mutated the only close homolog of easP in the M. brunneum genome, a gene we named estA. An easP/estA double mutant did not differ from the easP mutant in lysergic acid amide accumulation, indicating estA had no role in the pathway. We conclude EasP contributes to LAH accumulation but is not absolutely required. Either a gene encoding redundant function and lacking sequence identity with easP resides outside the ergot alkaloid synthesis gene cluster, or EasP plays an accessory role in the synthesis of LAH.


Subject(s)
Ergot Alkaloids , Metarhizium , Ergot Alkaloids/genetics , Ergot Alkaloids/metabolism , Lysergic Acid Diethylamide/analogs & derivatives , Metarhizium/genetics , Metarhizium/metabolism
3.
Psychopharmacology (Berl) ; 239(6): 1783-1796, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35487983

ABSTRACT

BACKGROUND: Novel psychedelics (NPs) are an expanding set of compounds, presenting new challenges for drug policy and opportunities for clinical research. Unlike their classical derivatives, little is known regarding their use profiles or their subjective effects. AIMS: The purpose of this study was to compile usage patterns and adverse event rates for individual NPs belonging to each of three main psychedelic structural families. Targeting the most widely used representatives for each class, we expanded on their phenomenological distinctions. METHODS: A two-part survey was employed. We investigated the prevalence of novel phenethylamines, tryptamine and lysergamides in NP users (N = 1180), contrasting the type and incidence of adverse events (AEs) using a set of logistic regressions. Honing in on 2-4-Bromo-2,5-dimethoxyphenyl)ethanamine (2C-B) (48.6%), 1-propionyl-lysergic acid diethylamide (1P-LSD) (34.2%) and 4-Acetoxy-N,N-dimethyltryptamine (4-AcO-DMT) (23.1%), we examined their phenomenological separability using a gradient boosting (XGBoost) supervised classifier. RESULTS: Novel phenethylamines had the highest prevalence of use (61.5%) seconded by tryptamines (43.8%) and lysergamides (42.9%). Usage patterns were identified for 32 different compounds, demonstrating variable dosages, durations and a common oral route of administration. Compared to phenethylamines, the odds for tryptamines and lysergamides users were significantly less for overall physical AEs. No significant differences in overall psychological AEs were found. Overall model area under the curve (AUC) stood at 0.79 with sensitivity (50.0%) and specificity (60.0%) for 2C-B ranking lowest. CONCLUSION: NP classes may hold distinct AE rates and phenomenology, the latter potentially clouded by the subjective nature of these experiences. Further targeted research is warranted.


Subject(s)
Hallucinogens , Hallucinogens/chemistry , Hallucinogens/pharmacology , Humans , Lysergic Acid Diethylamide/analogs & derivatives , Phenethylamines , Tryptamines
5.
Drug Test Anal ; 14(3): 545-556, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34022102

ABSTRACT

Lysergic acid diethylamide (LSD) is a potent psychoactive substance that has attracted great interest in clinical research. As the pharmacological exploration of LSD analogs continues to grow, some of those analogs have appeared on the street market. Given that LSD analogs are uncontrolled in many jurisdictions, it is important that these analogs be differentiated from LSD. This report presents the analysis of blotters found to contain the N-methyl-N-isopropyl isomer of LSD (MIPLA), and techniques to differentiate it from LSD and the N-methyl-N-propyl isomer (LAMPA) under routine conditions. Gas chromatography (GC)-solid phase infrared spectroscopy was particularly helpful. GC-electron ionization-tandem mass spectrometry of the m/z 72 iminium ion also provided sufficient information to distinguish the three isomers on mass spectral grounds alone, where chromatographic separation proved challenging. Derivatization with 2,2,2-trifluoro-N,N-bis (trimethylsilyl)acetamide (BSTFA) also led to improved GC separation. Liquid chromatography single quadrupole mass spectrometry (LC-Q-MS) and in-source collision-induced dissociation allowed for the differentiation between MIPLA and LAMPA based on distinct m/z 239 ion ratios when co-eluting. An alternative LC-MS/MS method improved the separation between all three lysergamides, but LSD was found to co-elute with iso-LSD. However, a comparison of ion ratios recorded for transitions at m/z 324.2 > 223.2 and m/z 324.2 > 208.2 facilitated their differentiation. The analysis of two blotters by LC-Q-MS revealed the presence of 180 and 186 µg MIPLA per blotter. These procedures may be used to avoid inadvertent misidentification of MIPLA or LAMPA as LSD.


Subject(s)
Lysergic Acid Diethylamide , Tandem Mass Spectrometry , Chromatography, Liquid , Gas Chromatography-Mass Spectrometry/methods , Lysergic Acid Diethylamide/analogs & derivatives
6.
Mikrochim Acta ; 188(12): 419, 2021 11 15.
Article in English | MEDLINE | ID: mdl-34782919

ABSTRACT

Yolk-shell structure magnetic metal-organic framework nanoparticles were prepared via post solvothermal method and employed as a magnetic solid-phase extraction adsorbent for selective pre-concentration of 5'-ribonucleotides by π stacking interaction, hydrogen bonding, and the strong interaction between titanium ions (Ti4+) and phosphate group. The properties of the materials were confirmed by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectrometry, vibrating sample magnetometer, infrared spectroscopy, thermogravimetric analysis, and Brunauer-Emmett-Teller analysis. The main parameters affecting the adsorption-desorption process, including adsorbent amount, incubation time, incubation temperature, sample pH, shaking speed, elution solution, and elution time, were systematically optimized. Finally, 1.0 mg of adsorbent mixed with 1.0 mL sample solution (10.0 mmol⋅L-1 NaCl, pH 3.0) and shaken at 135 rpm for 5 min at 40 °C, washed with 1.0 mL Na3PO4-NH3∙H2O under vortex for 5 min were selected as optimized adsorption-desorption conditions. The binding performance of adsorbent towards five nucleotides was evaluated by static adsorption experiments. The data are well-fitted to the Langmuir isotherm model and the maximum adsorption capacity is 27.8 mg g-1 for adenosine 5'-monophosphate. The limit of detection of the method is 19.44-38.41 ng mL-1. Under the optimal conditions, the adsorbent was successfully applied to magnetic solid-phase extraction and high performance liquid chromatography determination of five nucleotides in octopus, chicken, fish, and pork samples.


Subject(s)
Chromatography, High Pressure Liquid/methods , Lysergic Acid Diethylamide/analogs & derivatives , Magnetite Nanoparticles/chemistry , Metal-Organic Frameworks/chemistry , Nucleotides/chemistry , Lysergic Acid Diethylamide/chemistry
7.
Appl Environ Microbiol ; 87(24): e0180121, 2021 11 24.
Article in English | MEDLINE | ID: mdl-34586904

ABSTRACT

Ergot alkaloids derived from lysergic acid have impacted humanity as contaminants of crops and as the bases of pharmaceuticals prescribed to treat dementia, migraines, and other disorders. Several plant-associated fungi in the Clavicipitaceae produce lysergic acid derivatives, but many of these fungi are difficult to culture and manipulate. Some Aspergillus species, which may be more ideal experimental and industrial organisms, contain an alternate branch of the ergot alkaloid pathway, but none were known to produce lysergic acid derivatives. We mined the genomes of Aspergillus species for ergot alkaloid synthesis (eas) gene clusters and discovered that three species, A. leporis, A. homomorphus, and A. hancockii, had eas clusters indicative of the capacity to produce a lysergic acid amide. In culture, A. leporis, A. homomorphus, and A. hancockii produced lysergic acid amides, predominantly lysergic acid α-hydroxyethylamide (LAH). Aspergillus leporis and A. homomorphus produced high concentrations of LAH and secreted most of their ergot alkaloid yield into the culture medium. Phylogenetic analyses indicated that genes encoding enzymes leading to the synthesis of lysergic acid were orthologous to those of the lysergic acid amide-producing Clavicipitaceae; however, genes to incorporate lysergic acid into an amide derivative evolved from different ancestral genes in the Aspergillus species. Our data demonstrate that fungi outside the Clavicipitaceae produce lysergic acid amides and indicate that the capacity to produce lysergic acid evolved once, but the ability to insert it into LAH evolved independently in Aspergillus species and the Clavicipitaceae. The LAH-producing Aspergillus species may be useful for the study and production of these pharmaceutically important compounds. IMPORTANCE Lysergic acid derivatives are specialized metabolites with historical, agricultural, and medical significance and were known heretofore only from fungi in one family, the Clavicipitaceae. Our data show that several Aspergillus species, representing a different family of fungi, also produce lysergic acid derivatives and that the ability to put lysergic acid into its amide forms evolved independently in the two lineages of fungi. From microbiological and pharmaceutical perspectives, the Aspergillus species may represent better experimental and industrial organisms than the currently employed lysergic acid producers of the plant-associated Clavicipitaceae. The observation that both lineages independently evolved the derivative lysergic acid α-hydroxyethylamide (LAH), among many possible lysergic acid amides, suggests selection for this metabolite.


Subject(s)
Amides/chemistry , Aspergillus/chemistry , Lysergic Acid , Aspergillus/genetics , Biological Evolution , Hypocreales , Lysergic Acid/chemistry , Lysergic Acid Diethylamide/analogs & derivatives , Phylogeny
8.
Toxins (Basel) ; 13(7)2021 07 15.
Article in English | MEDLINE | ID: mdl-34357964

ABSTRACT

In the past centuries consumption of bread made of ergot-infected flour resulted in mass poisonings and miscarriages. The reason was the sclerotia of Claviceps purpurea (Fr.) Tul.-a source of noxious ergot alkaloids (ergotamine and ergovaline). The authors have searched the 19th century medical literature in order to find information on the following topics: dosage forms of drugs based on ergot and their application in official gynecology and obstetrics. The authors also briefly address the relevant data from the previous periods as well as the 20th century research on ergot. The research resulted in a conclusion that applications of ergot in gynecology and obstetrics in the 19th century were limited to controlling excessive uterine bleeding and irregular spasms, treatment of fibrous tumors of the uterus, and prevention of miscarriage, abortion, and amenorrhoea. The most common dosage forms mentioned in the works included in our review were the following: tinctures, water extracts (Wernich's and Squibb's watery extract of ergot), pills, and powders. The information documented in this paper will be helpful for further research and helpful in broadening the understanding of the historical application of the described controversial crude drugs. Ergot alkaloids were widely used in obstetrics, but in modern times they are not used in developed countries anymore. They may, however, play a significant role in developing countries where, in some cases, they can be used as an anti-hemorrhage agent during labor.


Subject(s)
Ergot Alkaloids/therapeutic use , Claviceps , Ergotamine , Ergotamines , Gynecology , Lysergic Acid Diethylamide/analogs & derivatives , Obstetrics
9.
Alkaloids Chem Biol ; 85: 1-112, 2021.
Article in English | MEDLINE | ID: mdl-33663751

ABSTRACT

While the use of ergot alkaloids in folk medicine has been practiced for millennia, systematic investigations on their therapeutic potential began about 100 years ago. Subsequently, Albert Hofmann's discovery of lysergic acid diethylamide (LSD) and its intense psychedelic properties garnered worldwide attention and prompted further studies of this compound class. As a result, several natural ergot alkaloids were discovered and unnatural analogs were synthesized, and some were used to treat an array of maladies, including Alzheimer's and Parkinson's disease. While LSD was never commercially approved, recent clinical studies have found it can be an innovative and effective treatment option for several psychiatric disorders. Ongoing biosynthetic and total synthetic investigations aim to understand the natural origins of ergot alkaloids, help develop facile means to produce these natural products and enable their continued use as medicinal chemistry lead structures. This review recounts major developments over the past 20 years in biosynthetic, total synthetic, and pharmaceutical studies. Many ergot alkaloid biosynthetic pathways have been elucidated, with some of them subsequently applied toward "green" syntheses. New chemical methodologies have fostered a fast and efficient access to the ergoline scaffold, prompting some groups to investigate biological properties of natural product-like ergot alkaloids. Limited pharmaceutical applications have yet to completely bypass the undesirable side effects of ergotism, suggesting further studies of this drug class are likely needed and will potentially harness major therapeutic significance.


Subject(s)
Chemistry, Pharmaceutical/history , Ergot Alkaloids/chemistry , Ergot Alkaloids/chemical synthesis , Amides/chemistry , Animals , Chemistry Techniques, Synthetic , Chemistry, Pharmaceutical/trends , Dopamine Agonists/chemistry , Ergolines/metabolism , Green Chemistry Technology , Hallucinogens/chemical synthesis , Hallucinogens/chemistry , Heterocyclic Compounds, 4 or More Rings/chemistry , History, 20th Century , History, 21st Century , Humans , Lysergic Acid Diethylamide/analogs & derivatives , Lysergic Acid Diethylamide/chemistry , Mental Disorders/drug therapy
10.
Int J Mol Sci ; 21(24)2020 Dec 21.
Article in English | MEDLINE | ID: mdl-33371302

ABSTRACT

Synthesis of the MIL-100 metal-organic framework particles was carried out by hydrothermal (HT) and microwave (MW)-assisted methods. Transmission electron microscopy showed formation of microparticles in the course of hydrothermal synthesis and nanoparticles for microwave-assisted synthesis. Powder X-ray diffraction confirmed formation of larger crystallites for hydrothermal synthesis. Particle aggregation in aqueous solution was observed by dynamic light scattering. However, the stability of both samples could be improved in acetic acid solution. Nitrogen sorption isotherms showed high porosity of the particles. ᶫ-leucine molecule was used as a model molecule for loading in the porous micro- and nanoparticles. Loading was estimated by FTIR spectroscopy and thermogravimetric analysis. UV-VIS spectroscopy quantified ᶫ-leucine release from the particles in aqueous solution. Cytotoxicity studies using the HeLa cell model showed that the original particles were somewhat toxic, but ᶫ-leucine loading ameliorated the toxic effects, likely due to signaling properties of the amino acid.


Subject(s)
Drug Carriers/chemistry , Drug Delivery Systems , Leucine/chemistry , Lysergic Acid Diethylamide/analogs & derivatives , Metal-Organic Frameworks/chemistry , Nanoparticles/administration & dosage , Cell Proliferation , HeLa Cells , Humans , Lysergic Acid Diethylamide/chemistry , Lysergic Acid Diethylamide/pharmacology , Nanoparticles/chemistry
11.
Yakugaku Zasshi ; 140(11): 1405-1413, 2020.
Article in Japanese | MEDLINE | ID: mdl-33132277

ABSTRACT

Lysergic acid diethylamide (LSD) is a hallucinogen, synthesized from ergot alkaloid, and controlled as a narcotic in Japan. Recently, LSD derivatives have appeared as designer drugs, all over the world. In previous study, we reported identification and analysis of four LSD derivatives in four paper sheet products. In this study, we detected three additional LSD derivatives from three paper sheet products, which were obtained from September 2019 to March 2020 in Japan. We extracted the compounds from paper sheet products with methanol for LC-MS, high-resolution MS and GC-MS analyses. The compounds were identified as 4-cyclopropionyl-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (1cP-LSD), N-methyl-N-isopropyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo-[4,3-fg]quinoline-9-carboxamide (MIPLA), 4-butyryl-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (1B-LSD), by GC-MS, LC-MS, LC-Q-TOF-MS and NMR analyses. As well as other N1-acylated LSD derivatives, 1cP-LSD and 1B-LSD were easily deacylated to LSD during GC-MS analysis, we have to be careful to analyze these compounds.


Subject(s)
Designer Drugs/analysis , Hallucinogens/isolation & purification , Illicit Drugs/analysis , Lysergic Acid Diethylamide/analogs & derivatives , Lysergic Acid Diethylamide/isolation & purification , Chromatography, Liquid , Dosage Forms , Gas Chromatography-Mass Spectrometry , Hallucinogens/analysis , Lysergic Acid Diethylamide/analysis , Magnetic Resonance Spectroscopy , Mass Spectrometry , Paper
12.
Yakugaku Zasshi ; 140(5): 739-750, 2020.
Article in Japanese | MEDLINE | ID: mdl-32378678

ABSTRACT

To prevent the abuse of new psychoactive substances (NPS), a total of 2372 substances and two plants are controlled as "Designated Substances" in Japan as of September 2019. Although the distribution of these substances has decreased for the past three years, newly-emerged NPS are still being found. In this study, we detected four lysergic acid diethylamide (LSD) derivatives as designer drugs from four paper sheet products, which were obtained from 2014 to 2017 in Japan. The compounds were identified as 4-Acetyl-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (ALD-52), N,N,7-triethyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (ETH-LAD), 7-Allyl-N,N-diethyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (AL-LAD), N,N-diethyl-7-methyl-4-propionyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (1P-LSD), by GC-MS, LC-MS, LC-Q-TOF-MS and NMR analyses. Further, we studied the extraction methods of LSD derivatives from paper sheet, and the analytical conditions of GC-MS, LC-MS and LC-FL(fluorescence). Among LSD derivatives, 1P-LSD have been controlled as designated substances (Shitei Yakubutsu) under the Pharmaceutical and Medical Device Act in Japan since April 2016. For the legislation of the other derivatives identified in this study, the evaluation of their pharmacological properties are now in progress.


Subject(s)
Designer Drugs/analysis , Illicit Drugs/analysis , Lysergic Acid Diethylamide/analysis , Paper , Chromatography, Liquid/methods , Gas Chromatography-Mass Spectrometry/methods , Lysergic Acid Diethylamide/analogs & derivatives , Lysergic Acid Diethylamide/chemistry , Magnetic Resonance Spectroscopy/methods , Mass Spectrometry/methods , Spectrometry, Fluorescence/methods
13.
J Colloid Interface Sci ; 574: 364-376, 2020 Aug 15.
Article in English | MEDLINE | ID: mdl-32339819

ABSTRACT

Iron-based metal-organic frameworks (MOFs) with low cost and excellent photocatalytic potential are extremely attractive in the field of energy utilization and environmental remediation. In this study, a novel In2S3/MIL-100(Fe) photocatalyst was successfully synthesized by a facile solvothermal method for the first time. Several technologies (such as X-ray diffraction, scanning electron microscope, transmission electron microscope, and X-ray photoelectron spectroscopy) were used to characterize the as-obtained samples and demonstrate the successful combination of MIL-100(Fe) and In2S3. Experimental results showed that 18% of tetracycline (TC) was adsorbed under dark condition and another 70% of TC was degraded under visible-light irradiation when treating 100 mL of TC solution (10 mg/L) with 30 mg of In2S3/MIL-100(Fe) composites. The corresponding TC removal efficiency was almost 1.9 and 1.6 times higher than that of pure MIL-100(Fe) and In2S3, respectively. The mechanism investigations revealed that the heterojunction composite exhibited superior charge transfer than either MIL-100(Fe) or In2S3, and this caused more efficient separation of electron-hole pairs. As a result, more radicals and holes were generated in the composite, leading to better photocatalytic performance. This work highlights the powerful combination of MOFs and semiconductor, which is a promising approach to fabricate heterojunction photocatalyst for wastewater purification.


Subject(s)
Iron/chemistry , Light , Lysergic Acid Diethylamide/analogs & derivatives , Metal-Organic Frameworks/chemistry , Photochemical Processes/radiation effects , Tetracycline/chemistry , Catalysis/radiation effects , Lysergic Acid Diethylamide/chemistry , Particle Size , Surface Properties
14.
J Colloid Interface Sci ; 571: 275-284, 2020 Jul 01.
Article in English | MEDLINE | ID: mdl-32203764

ABSTRACT

The uniform tablet-like TiO2/C nanocomposites with two crystal types (rutile and anatase) and large specific surface area (438 m2 g-1) were successfully prepared by Materials of Institut Lavoisier-125(Ti) (MIL-125(Ti)) calcined at a suitable temperature and applied for photocatalytic tetracycline (TC). The nanocomposites were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and mapping, N2 adsorption-desorption isotherms, photoluminescence spectra (PL), photocurrent, and X-ray photoelectron spectroscopy (XPS). The changes of physicochemical parameters are discussed in detail. It is found that nanocomposite through suitable calcination temperature (M-A-800) with large surface area and appropriate micropore/mesopore ratio could strengthen separation and migration rates of photo-generated charge, resulting in the improvement of visible light photocatalytic activity of tetracycline, and exhibited about 2.0 times quicker than that of MIL-125(Ti). In addition, M-A-800 displayed favourable reusability and stability in four circulation tests. Finally, the reaction mechanism of photocatalyst and photodegradation pathway of tetracycline was also proposed. O2- was the most important active species, and dehydroxylation and decarboxylation were the main photodegradation pathway of tetracycline.


Subject(s)
Carbon/chemistry , Light , Lysergic Acid Diethylamide/analogs & derivatives , Organometallic Compounds/chemistry , Tetracycline/chemistry , Titanium/chemistry , Lysergic Acid Diethylamide/chemistry , Particle Size , Photolysis , Surface Properties
15.
Drug Test Anal ; 12(6): 812-826, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32180350

ABSTRACT

Lysergic acid diethylamide (LSD) is a prototypical serotonergic psychedelic drug and the subject of many clinical investigations. In recent years, a range of lysergamides has emerged with the production of some being inspired by the existing scientific literature. Others, for example various 1-acyl substituted lysergamides, did not exist before their appearance as research chemicals. 1-Cylopropanoyl-LSD (1CP-LSD) has recently emerged as a new addition to the group of lysergamide-based designer drugs and is believed to be psychoactive in humans. In this investigation, 1CP-LSD was subjected to detailed analytical characterizations including various mass spectrometry (MS) platforms, gas and liquid chromatography, nuclear magnetic resonance spectroscopy, solid phase and GC condensed phase infrared spectroscopy. Analysis by GC-MS also revealed the detection of artificially induced degradation products. Incubation of 1CP-LSD with human serum led to the formation of LSD, indicating that it may act as a prodrug for LSD in vivo, similar to other 1-acyl substituted lysergamides. The analysis of blotters and pellets is also included. 1CP-LSD also induces the head-twitch response (HTR) in C57BL/6 J mice, indicating that it produces an LSD-like behavioural profile. 1CP-LSD induced the HTR with an ED50 = 430.0 nmol/kg which was comparable to 1P-LSD (ED50 = 349.6 nmol/kg) investigated previously. Clinical studies are required to determine the potency and profile of the effects produced by 1CP-LSD in humans.


Subject(s)
Designer Drugs/pharmacology , Hallucinogens/pharmacology , Lysergic Acid Diethylamide/analogs & derivatives , Lysergic Acid Diethylamide/pharmacology , Quinolines/pharmacology , Animals , Behavior, Animal/drug effects , Chromatography, Liquid , Designer Drugs/chemistry , Gas Chromatography-Mass Spectrometry , Hallucinogens/blood , Hallucinogens/chemistry , Lysergic Acid Diethylamide/blood , Lysergic Acid Diethylamide/chemistry , Magnetic Resonance Spectroscopy , Male , Mice , Mice, Inbred C57BL , Prodrugs , Quinolines/blood , Quinolines/chemistry , Spectrophotometry, Infrared , Tandem Mass Spectrometry
16.
J Colloid Interface Sci ; 570: 163-172, 2020 Jun 15.
Article in English | MEDLINE | ID: mdl-32146243

ABSTRACT

Extensive exposure to antibiotics could potentially be harmful to the environment and human health. The development of effective and convenient technologies to remove residual antibiotics from water is imperative. Herein, we successfully developed a facile method via pyrolysis of Fe-MIL-88B_NH2 to synthesize magnetic nanocomposites (MNC) as potential adsorbents, which exhibited cluster-shape structure and excellent magnetic response. Magnetic nanocomposites carbonized at 700 °C showed high efficiency for sulfamethoxazole (SMX) adsorption (73.53 mg/g). Some experimental conditions including solution pH, ionic strength, coexisting ions and SMX concentration were systematically investigated. The adsorption isotherm and kinetic followed Langmuir and the pseudo-second-order models, and the adsorption process was dependent on the solution pH. The adsorption mechanism hypothesis was pore filling effect, π-π EDA and electrostatic interactions. Moreover, MNC-700 exhibited good reusability and magnetic separation properties, being reused six times without significant loss in adsorption capacity.


Subject(s)
Iron/chemistry , Lysergic Acid Diethylamide/analogs & derivatives , Metal-Organic Frameworks/chemistry , Sulfamethoxazole/isolation & purification , Water Pollutants, Chemical/isolation & purification , Lysergic Acid Diethylamide/chemistry , Magnetic Fields , Metal-Organic Frameworks/chemical synthesis , Nanocomposites/chemistry , Particle Size , Solutions , Sulfamethoxazole/chemistry , Surface Properties , Water/chemistry , Water Pollutants, Chemical/chemistry
18.
Neuropharmacology ; 172: 107856, 2020 08 01.
Article in English | MEDLINE | ID: mdl-31756337

ABSTRACT

The ergoline d-lysergic acid diethylamide (LSD) is one of the most potent psychedelic drugs. 1-Acetyl-LSD (ALD-52), a derivative of LSD containing an acetyl group on the indole nitrogen, also produces psychedelic effects in humans and has about the same potency as LSD. Recently, several other 1-acyl-substitued LSD derivatives, including 1-propanoyl-LSD (1P-LSD) and 1-butanoyl-LSD (1B-LSD), have appeared as designer drugs. Although these compounds are assumed to act as prodrugs for LSD, studies have not specifically tested this prediction. The present investigation was conducted to address the gap of information about the pharmacological effects and mechanism-of-action of 1-acyl-substituted LSD derivatives. Competitive binding studies and calcium mobilization assays were performed to assess the interaction of ALD-52, 1P-LSD, and 1B-LSD with serotonin 5-HT2 receptor subtypes. A receptorome screening was performed with 1B-LSD to assess its binding to other potential targets. Head twitch response (HTR) studies were performed in C57BL/6J mice to assess in vivo activation of 5-HT2A (the receptor thought to be primarily responsible for hallucinogenesis). Finally, liquid chromatography/ion-trap mass spectrometry (LC/MS) was used to quantify plasma levels of LSD in Sprague-Dawley rats treated with ALD-52 and 1P-LSD. 1-Acyl-substitution reduced the affinity of LSD for most monoamine receptors, including 5-HT2A sites, by one to two orders of magnitude. Although LSD acts as an agonist at 5-HT2 subtypes, ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists in Ca2+-mobilization assays. Despite the detrimental effect of 1-acyl substitution on 5-HT2A affinity and efficacy, 1-acyl-substitued LSD derivatives induce head twitches in mice with relatively high potency. High levels of LSD were detected in the plasma of rats after subcutaneous administration of ALD-52 and 1P-LSD, demonstrating these compounds are rapidly and efficiently deacylated in vivo. These findings are consistent with the prediction that ALD-52, 1P-LSD and 1B-LSD serve as prodrugs for LSD. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.


Subject(s)
Hallucinogens/pharmacology , Lysergic Acid Diethylamide/analogs & derivatives , Lysergic Acid Diethylamide/pharmacology , Prodrugs/pharmacology , Animals , Behavior, Animal/drug effects , Binding, Competitive/drug effects , Biotransformation , Calcium Signaling/drug effects , Drug Evaluation, Preclinical , Hallucinogens/pharmacokinetics , Lysergic Acid Diethylamide/pharmacokinetics , Male , Mice , Mice, Inbred C57BL , Prodrugs/chemical synthesis , Prodrugs/pharmacokinetics , Rats , Rats, Sprague-Dawley , Receptors, Serotonin, 5-HT2/drug effects , Serotonin 5-HT2 Receptor Agonists/pharmacology , Serotonin 5-HT2 Receptor Antagonists/pharmacology
19.
Sci Total Environ ; 699: 134375, 2020 Jan 10.
Article in English | MEDLINE | ID: mdl-31677465

ABSTRACT

In order to solve the problems of short residence time and low diffusion of CO2 gas in microalgal solution, calcinated metal-organic framework MIL-100(Fe) were first used as CO2 adsorbents to promote the growth of Arthrospira platensis cells by increasing carbon fixation. The adsorbent (MIL-100(Fe)-4 h) containing unsaturated metal sites, improved the conversion of CO2 to dissolved inorganic carbon by 52.3% and concentration of HCO3- by 20.0% in culture medium, as compared to the medium without CO2 adsorbent added. The increased HCO3- concentration facilitated carboxysome accumulation (increased to 21.7 times) to activate the photosynthetic Calvin cycle in Arthrospira cells. The increased cell growth rate promoted cell volume by 132% and knot length by 102%, while the fractal dimension of the cell surface decreased by 13.5%. The biomass productivity of Arthrospira cells cultivated with the CO2 adsorbent MIL-100(Fe)-4 h remarkably increased by 81.9%.


Subject(s)
Spirulina/physiology , Biomass , Carbon Cycle , Carbon Dioxide/metabolism , Lysergic Acid Diethylamide/analogs & derivatives , Lysergic Acid Diethylamide/metabolism
20.
Drug Test Anal ; 12(4): 465-471, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31846172

ABSTRACT

Due to the much lower production costs but similar effects to lysergic acid diethylamide (LSD), phenethylamine derivatives are sold as a cheaper replacement or deceptively as LSD itself. These potent hallucinogenic substances can lead to severe intoxication, thus a more profound understanding of their use is required. This includes the elucidation of the manufacturing processes for the commonly used blotter papers and the assessment of the risk of overdosing because of a heterogeneous distribution on the blotter papers. Besides the rapid detection of the analytes, the manufacturing process was elucidated by three different imaging techniques and liquid chromatography-mass spectrometry (LC-MS). A blotter paper sample, containing the two hallucinogenic phenethylamine derivatives 25I-NBOMe and 25C-NBOMe, was analyzed by complementary techniques such as micro x-ray fluorescence (µXRF), laser ablation (LA)-inductively coupled plasma-optical emission spectroscopy (ICP-OES), matrix assisted laser desorption ionization (MALDI)-MS, and with LC-MS after extraction. Using the signal from chlorine and iodine within the compounds, µXRF proved to be the fastest, cheapest and easiest method for identification, requiring no sample preparation at all. LA-ICP-OES provided three-dimensional information of the elements in the blotter paper. These results helped to confirm the assumption that manufacturers spray the compounds onto the paper. Whereas µXRF and LA-ICP-OES detected signals for chlorine and iodine, MALDI-MS-imaging showed the molecular distribution of both analytes. LC-MS analyses as a complementary method support the imaging results. Quantitative results for different drug hotspots revealed a heterogeneous distribution of the drugs on the blotter paper implying an inherent risk of overdosing for consumers.


Subject(s)
Benzylamines/analysis , Dimethoxyphenylethylamine/analogs & derivatives , Hallucinogens/analysis , Paper , Phenethylamines/analysis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Chromatography, High Pressure Liquid/methods , Dimethoxyphenylethylamine/analysis , Lysergic Acid Diethylamide/analogs & derivatives
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