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1.
Simon D. Brandt Pierce V. Kavanagh Folker Westphal Alexander Stratford Simon P. Elliott Geraldine Dowling Jason Wallach Adam L. Halberstadt 《Drug testing and analysis》2019,11(8):1122-1133
The psychedelic properties of lysergic acid diethylamide (LSD) have captured the imagination of researchers for many years and its rediscovery as an important research tool is evidenced by its clinical use within neuroscientific and therapeutic settings. At the same time, a number of novel LSD analogs have recently emerged as recreational drugs, which makes it necessary to study their analytical and pharmacological properties. One recent addition to this series of LSD analogs is 1‐butanoyl‐LSD (1B‐LSD), a constitutional isomer of 1‐propanoyl‐6‐ethyl‐6‐nor‐lysergic acid diethylamide (1P‐ETH‐LAD), another LSD analog that was described previously. This study presents a comprehensive analytical characterization of 1B‐LSD employing nuclear magnetic resonance spectroscopy (NMR), low‐ and high‐resolution mass spectrometry platforms, gas‐ and liquid chromatography (GC and LC), and GC‐condensed phase and attenuated total reflection infrared spectroscopy analyses. Analytical differentiation of 1B‐LSD from 1P‐ETH‐LAD was straightforward. LSD and other serotonergic hallucinogens induce the head‐twitch response (HTR) in rats and mice, which is believed to be mediated largely by 5‐HT2A receptor activation. HTR studies were conducted in C57BL/6J mice to assess whether 1B‐LSD has LSD‐like behavioral effects. 1B‐LSD produced a dose‐dependent increase in HTR counts, acting with ~14% (ED50 = 976.7 nmol/kg) of the potency of LSD (ED50 = 132.8 nmol/kg). This finding suggests that the behavioral effects of 1B‐LSD are reminiscent of LSD and other serotonergic hallucinogens. The possibility exists that 1B‐LSD serves as a pro‐drug for LSD. Further investigations are warranted to confirm whether 1B‐LSD produces LSD‐like psychoactive effects in humans. 相似文献
2.
Return of the lysergamides. Part I: Analytical and behavioural characterization of 1‐propionyl‐d‐lysergic acid diethylamide (1P‐LSD) 下载免费PDF全文
Simon D. Brandt Pierce V. Kavanagh Folker Westphal Alexander Stratford Simon P. Elliott Khoa Hoang Jason Wallach Adam L. Halberstadt 《Drug testing and analysis》2016,8(9):891-902
1‐Propionyl‐d‐lysergic acid diethylamide hemitartrate (1P‐LSD) has become available as a ‘research chemical’ in the form of blotters and powdered material. This non‐controlled derivative of d‐lysergic acid diethylamide (LSD) has previously not been described in the published literature despite being closely related to 1‐acetyl‐LSD (ALD‐52), which was developed in the 1950s. This study describes the characterization of 1P‐LSD in comparison with LSD using various chromatographic and mass spectrometric methods, infrared and nuclear magnetic resonance spectroscopy. An important feature common to LSD and other serotonergic hallucinogens is that they produce 5‐HT2A‐receptor activation and induce the head‐twitch response (HTR) in rats and mice. In order to assess whether 1P‐LSD displays LSD‐like properties and activates the 5‐HT2A receptor, male C57BL/6 J mice were injected with vehicle (saline) or 1P‐LSD (0.025–0.8 mg/kg, IP) and HTR assessed for 30 min using magnetometer coil recordings. It was found that 1P‐LSD produced a dose‐dependent increase in HTR counts, and that it had ~38% (ED50 = 349.6 nmol/kg) of the potency of LSD (ED50 = 132.8 nmol/kg). Furthermore, HTR was abolished when 1P‐LSD administration followed pretreatment with the selective 5‐HT2A receptor antagonist M100907 (0.1 mg/kg, SC), which was consistent with the concept that the behavioural response was mediated by activation of the 5‐HT2A receptor. These results indicate that 1P‐LSD produces LSD‐like effects in mice, consistent with its classification as a serotonergic hallucinogen. Nevertheless, the extent to which 1P‐LSD might show psychoactive effects in humans similar to LSD remains to be investigated. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
3.
Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM‐775) 下载免费PDF全文
Simon D. Brandt Pierce V. Kavanagh Brendan Twamley Folker Westphal Simon P. Elliott Jason Wallach Alexander Stratford Landon M. Klein John D. McCorvy David E. Nichols Adam L. Halberstadt 《Drug testing and analysis》2018,10(2):310-322
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. 相似文献
4.
Simon D. Brandt Pierce V. Kavanagh Folker Westphal Benedikt Pulver Kathleen Morton Alexander Stratford Geraldine Dowling Adam L. Halberstadt 《Drug testing and analysis》2022,14(4):733-740
The psychopharmacological properties of the psychedelic drug lysergic acid diethylamide (LSD) have attracted the interest of several generations of scientists. While further explorations involving novel LSD-type compounds are needed to assess their potential as medicinal drugs, the emergence of novel derivatives as recreational drugs has also been observed. 1-Valeroyl-LSD (also known as 1-valeryl-LSD, 1-pentanoyl-LSD, 1V-LSD, or “Valerie”) is a new N1-acylated LSD derivative that recently appeared on the online market, and it could be viewed as a higher homolog of ALD-52, 1P-LSD, and 1B-LSD. The present study included the analytical characterization and involved various methods of mass spectrometry (MS), gas and liquid chromatography (GC and LC), nuclear magnetic resonance (NMR) spectroscopy, GC–solid-state infrared (GC-sIR) analysis, and Raman spectroscopy. The in vivo activity of 1V-LSD was assessed 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. Similar to LSD and other psychedelic drugs, the HTR induced by 1V-LSD was dose dependent, and the median effective dose for 1V-LSD was 373 nmol/kg, which was about a third of the potency of LSD (ED50 = 132.8 nmol/kg). Lysergamides containing the N1-substituent typically act as weak partial agonists at the 5-HT2A receptor and are believed to serve as prodrugs for LSD. 1V-LSD is also likely to be hydrolyzed to LSD and serve as a prodrug, but studies to assess the biotransformation and receptor pharmacology of 1V-LSD should be performed to fully elucidate its mechanism of action. 相似文献
5.
《Drug testing and analysis》2017,9(1):38-50
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, N 6‐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‐HT2A receptors. 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. 相似文献
6.
《Drug testing and analysis》2017,9(10):1641-1649
The psychoactive properties of lysergic acid diethylamide (LSD) have fascinated scientists across disciplines and the exploration of other analogues and derivatives has been motivated by deepening the understanding of ligand‐receptor interactions at the molecular level as well as by the search for new therapeutics. Several LSD congeners have appeared on the new psychoactive substances (NPS) market in the form of blotters or powders. Examples include 1‐propionyl‐LSD (1P–LSD), AL‐LAD, and LSZ. The absence of analytical data for novel compounds is a frequent challenge encountered in clinical and toxicological investigations. Two newly emerging lysergamides, namely N6‐ethyl‐6‐norlysergic acid diethylamide (ETH‐LAD) and 1P–ETH‐LAD, were characterized by gas chromatography–mass spectrometry (GC–MS), low and high mass accuracy electrospray MS(/MS), GC solid‐state infrared analysis, high performance liquid chromatography diode array detection as well as nuclear magnetic resonance spectroscopy. Limited analytical data for ETH‐LAD were previously available, whereas information about 1P–ETH‐LAD has not previously been encountered in the scientific literature. This study extends the characterization of lysergamides distributed on the NPS market, which will help to make analytical data available to clinicians, toxicologists, and other stakeholders who are likely to encounter these substances. The analysis of a test incubation of 1P–ETH‐LAD with human serum at 37°C by LC single quadrupole MS at various time points (0–6 h, once per hour and one measurement after 24 h) revealed the formation of ETH‐LAD, suggesting that 1P–ETH‐LAD might serve as a pro‐drug. 1P–ETH‐LAD was still detectable in serum after 24 h. Copyright © 2017 John Wiley & Sons, Ltd. 相似文献
7.
Simon D. Brandt Pierce V. Kavanagh Folker Westphal Alexander Stratford Simon P. Elliott Geraldine Dowling Adam L. Halberstadt 《Drug testing and analysis》2020,12(10):1514-1521
Recent investigations have shown that N‐ethyl‐N‐cyclopropyl lysergamide (ECPLA) produces LSD‐like behavioral effects in mice, which suggests that it may act as a hallucinogen in humans. Although the use of ECPLA as a recreational drug has been limited, key analytical data that can be used to detect ECPLA are required for future forensic and clinical investigations. ECPLA is an isomer of (2′S,4′S)‐lysergic acid 2,4‐dimethylazetidide (LSZ), a lysergamide that emerged as a recreational drug in 2013. Several analytical approaches were examined, including single‐ and tandem mass spectrometry platforms at low and high resolution, gas‐ and liquid chromatography (GC, LC), nuclear magnetic resonance spectroscopy (NMR), and GC condensed‐phase infrared spectroscopy (GC‐sIR). ECPLA and LSZ could be differentiated by NMR, GC‐sIR, GC, and LC‐based methods. The electron ionization mass spectra of ECPLA and LSZ contained ion clusters typically observed with related lysergamides such as m/z 150–155, m/z 177–182, m/z 191–197, m/z 205–208, and m/z 219–224. One of the significant differences in abundance related to these clusters included ions at m/z 196 and m/z 207/208. The base peaks were detected at m/z 221 in both cases followed by the retro‐Diels‐Alder fragment at m/z 292. Minor but noticeable differences between the two isomers could also be seen in the relative abundance of m/z 98 and m/z 41. Electrospray ionization mass spectra included lysergamide‐related ions at m/z 281, 251, 223, 208, 197, 180, and 140. LSZ (but not ECPLA) showed product ions at m/z 267 and m/z 98 under the conditions used. 相似文献
8.
Simon D. Brandt Pierce V. Kavanagh Folker Westphal Benedikt Pulver Hannes M. Schwelm Kyla Whitelock Alexander Stratford Volker Auwärter Adam L. Halberstadt 《Drug testing and analysis》2022,14(8):1503-1518
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-8β-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. 相似文献
9.
Simon D. Brandt Pierce V. Kavanagh Folker Westphal Alexander Stratford Peter Blanckaert Geraldine Dowling Matthias Grill Hannes M. Schwelm Volker Auwärter Stephen J. Chapman 《Drug testing and analysis》2022,14(3):545-556
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. 相似文献
10.
Pierce V. Kavanagh Folker Westphal Benedikt Pulver Hannes M. Schwelm Alexander Stratford Volker Auwärter Stephen J. Chapman Adam L. Halberstadt Simon D. Brandt 《Drug testing and analysis》2023,15(3):277-291
The development of novel lysergamides continues to occur, based on both the needs of psychedelic medicine and commercial interest in new recreational substances. The present study continues the authors' research on novel lysergamides and describes the analytical profile of 1-cyclopropanoyl-AL-LAD (IUPAC name: 1-(cyclopropanecarbonyl)-N,N-diethyl-6-(prop-2-en-1-yl)-9,10-didehydroergoline-8β-carboxamide; 1cP-AL-LAD), using various chromatographic, mass spectrometric, and spectroscopic methods. Analysis of a powdered sample of 1cP-AL-LAD, obtained from an online vendor, by high performance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry in full scan/AutoMS/MS mode revealed the detection of 17 impurities based on high-resolution tandem mass spectral data; tentative determination of their identity was based on mass spectral grounds alone, though detection of AL-LAD and 1P-AL-LAD was confirmed using available reference standards. Other tentative compound identifications included 1-acetyl-AL-LAD and several other substances potentially reflecting oxidation of the N6-allyl group as well as other positions on the ergoline ring system. These data may assist those interested in the chemistry of lysergamides. Finally, 1cP-AL-LAD was also detected in samples of “blotters” sold online for recreational use. 相似文献
11.
Michael Dybek Jason Wallach Pierce V. Kavanagh Tristan Colestock Nadine Filemban Geraldine Dowling Folker Westphal Simon P. Elliott Adeboye Adejare Simon D. Brandt 《Drug testing and analysis》2019,11(8):1144-1161
A number of substances based on the 1,2‐diarylethylamine template have been investigated for various potential clinical applications whereas others have been encountered as research chemicals sold for non‐medical use. Some of these substances have transpired to function as NMDA receptor antagonists that elicit dissociative effects in people who use these substances recreationally. 1‐[1‐(2‐Fluorophenyl)‐2‐phenylethyl]pyrrolidine (fluorolintane, 2‐F‐DPPy) has recently appeared as a research chemical, which users report has dissociative effects. One common difficulty encountered by stakeholders confronting the appearance of new psychoactive substances is the presence of positional isomers. In the case of fluorolintane, the presence of the fluorine substituent on either the phenyl and benzyl moieties of the 1,2‐diarylethylamine structure results in a total number of six possible racemic isomers, namely 2‐F‐, 3‐F‐, and 4‐F‐DPPy (phenyl ring substituents) and 2”‐F‐, 3”‐F‐, and 4”‐F‐DPPy (benzyl ring substituents). The present study reports the chemical syntheses and comprehensive analytical characterizations of the two sets of three positional isomers. These studies included various low‐ and high‐resolution mass spectrometry platforms, gas‐ and liquid chromatography (GC and LC), nuclear magnetic resonance (NMR) spectroscopy and GC‐condensed phase and attenuated total reflection infrared spectroscopy analyses. The differentiation between each set of three isomers was possible under a variety of experimental conditions including GC chemical ionization triple quadrupole tandem mass spectrometric analysis of the [M + H – HF]+ species. The latter MS method was particularly helpful as it revealed distinct formations of product ions for each of the six investigated substances. 相似文献
12.
Structure–5‐HT Receptor Affinity Relationship in a New Group of 7‐Arylpiperazynylalkyl and 7‐Tetrahydroisoquinolinylalkyl Derivatives of 8‐Amino‐1,3‐dimethyl‐1H‐purine‐2,6(3H,7H)‐dione 下载免费PDF全文
Paweł Żmudzki Grażyna Chłoń‐Rzepa Andrzej J. Bojarski Małgorzata Zygmunt Grzegorz Kazek Barbara Mordyl Maciej Pawłowski 《Archiv der Pharmazie》2015,348(4):229-241
13.
《Journal of labelled compounds & radiopharmaceuticals》2004,47(9):591-598
Many people suffer from psychiatric illnesses like depression and anorexia. Relevant to these diseases is amongst others a malfunctioning of brain 5‐HT2A‐receptors. To allow in vivo quantification of these receptors with Single Photon Emission Computerized Tomography (SPECT), a radiolabelled ligand with high 5‐HT2A affinity is needed. This work reports the radiosynthesis of [123I]‐(4‐fluorophenyl) {1‐[2‐(2‐iodophenyl)ethyl]piperidin‐4‐yl}methanone, the synthesis of its precursor, (4‐fluorophenyl) {1‐[2‐(2‐bromophenyl)ethyl]piperidin‐4‐yl}methanone, and the preliminary in vivo evaluation of the tracer. The precursor was synthesized with a total yield of 40%. Radiolabelling was performed using a halogen exchange reaction and the yield was 70%. Radiochemical purity was >95%, and specific activity was at least 2.4 Ci/µmol. Log P was measured to be 2.52. The tracer showed uptake in mice brain (3.5% I.D./g tissue at 3 min post injection) and therefore will be evaluated further by regional brain biodistribution and displacement studies in rabbits. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
14.
Rationale The drug discrimination procedure is the most frequently used in vivo model of hallucinogen activity. Historically, most drug discrimination studies have been conducted in the rat. With the development of genetically modified mice, a powerful new tool has become available for investigating the mechanisms of drug-induced behavior. The current paper is part of an ongoing effort to determine the utility of the drug discrimination technique for evaluating hallucinogenic drugs in mice.Objective To establish the training procedures and characterize the stimulus properties of (+)lysergic acid diethylamide (LSD) in mice.Methods Using a two-lever drug discrimination procedure, C57Bl/6J mice were trained to discriminate 0.45 mg/kg LSD vs saline on a VI30 sec schedule of reinforcement, with vanilla-flavored Ensure serving as the reinforcer.Results As in rats, acquisition was orderly, but the training dose was nearly five-fold higher for mice than rats. LSD lever selection was dose-dependent. Time-course studies revealed a rapid loss of the LSD stimulus effects. The 5-HT2A/2C receptor agonist, 2,5-dimethoxy-4-bromoamphetamine [(–)DOB] (1.0 mg/kg), substituted fully for LSD and the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) (1.6 mg/kg), substituted partially for LSD. Pretreatment with the 5-HT2A receptor-selective antagonist, MDL 100907, or the 5-HT1A-selective antagonist WAY 100635, showed that each antagonist only partially blocked LSD discrimination. Substitution of 1.0 mg/kg (–)DOB for LSD was fully blocked by pretreatment with MDL 100907 but unaltered by WAY 100635 pretreatment.Conclusions These data suggest that in mice the stimulus effects of LSD have both a 5-HT2A receptor and a 5-HT1A receptor component. 相似文献
15.
Syntheses,analytical and pharmacological characterizations of the ‘legal high’ 4‐[1‐(3‐methoxyphenyl)cyclohexyl]morpholine (3‐MeO‐PCMo) and analogues 下载免费PDF全文
《Drug testing and analysis》2018,10(2):272-283
New psychoactive substances (NPS) are commonly referred to as ‘research chemicals’, ‘designer drugs’ or ‘legal highs’. One NPS class is represented by dissociative anesthetics, which include analogues of the arylcyclohexylamine phencyclidine (PCP), ketamine and diphenidine. A recent addition to the NPS market was 4‐[1‐(3‐methoxyphenyl)cyclohexyl]morpholine (3‐MeO‐PCMo), a morpholine analogue of 3‐MeO‐PCP. Although suspected to have dissociative effects in users, information about its pharmacological profile is not available. From clinical and forensic perspectives, detailed analytical data are needed for identification, especially when facing the presence of positional isomers, as these are frequently unavailable commercially. This study presents the analytical and pharmacological characterization of 3‐MeO‐PCMo along with five additional analogues, namely the 2‐ and 4‐MeO‐PCMo isomers, 3,4‐methylenedioxy‐PCMo (3,4‐MD‐PCMo), 3‐Me‐PCMo and PCMo. All six arylcyclohexylmorpholines were synthesized and characterized using chromatographic, mass spectrometric and spectroscopic techniques. The three positional isomers could be differentiated and the identity of 3‐MeO‐PCMo obtained from an internet vendor was verified. All six compounds were also evaluated for affinity at 46 central nervous system receptors including the N‐methyl‐d ‐aspartate receptor (NMDAR), an important target for dissociative anesthetics such as PCP and ketamine. In vitro binding studies using (+)‐[3‐3H]‐MK‐801 in rat forebrain preparations revealed moderate affinity for NMDAR in the rank order of 3‐Me >3‐MeO > PCMo >3,4‐MD > 2‐MeO > 4‐MeO‐PCMo. 3‐MeO‐PCMo was found to have moderate affinity for NMDAR comparable to that of ketamine, and had an approximate 12‐fold lower affinity than PCP. These results support the anecdotal reports of dissociative effects from 3‐MeO‐PCMo in humans. 相似文献
16.
Leila Hassanzadeh Mostafa Erfani Seyed Esmaeil Sadat Ebrahimi 《Journal of labelled compounds & radiopharmaceuticals》2012,55(10):371-376
To develop a novel 5HT1A receptor imaging agent, a new methoxyphenyl piperazine derivative was synthesized and radiolabeled with 99mTc‐tricarbonyl precursor. We used the Cu (I)‐catalyzed cycloaddition of azide and terminal alkynes to synthesize 1, 2, 3 triazole as the metal chelating system. This synthesis provided reliable and reproducible method to attach technetium to the methoxyphenyl piperazine moiety. 99mTc‐tricabonyl labeling of ligand was performed at high radiochemical purity (greater than 95%). The radiolabeled compound was stable at least 24 h in room temperature. In vitro stability study in human serum albumin showed more than 90% stability in 37 °C incubation for 6 h. Biodistribution studies in rat have shown brain hippocampus uptake of 0.31 ± 0.02 %ID/g at 5‐min post‐injection. The favorable in vitro/in vivo stability, lipophilicity, and biodistribution profiles suggest that this radioconjugate is a good candidate for further exploration of its potential clinical application. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
17.
Morphine and lysergic acid diethylamide (LSD) each was used as a discriminative stimulus for rats. After the injection of drug (morphine or LSD), depression of one lever of an operant test chamber resulted in positive reinforcement according to a variable interval schedule of 15 sec (VI-15 sec). When saline was given, responses on the opposite lever were reinforced. Discriminated responding occurred when either morphine or LSD served as the discriminative stimulus. When animals which were trained to d discriminate morphine from saline were given LSD, they pressed predominantly the saline-correct lever. Similarly, LSD discrimination did not generalize to morphine. Two 5-hydroxytryptamine (5-HT) antagonists, cyproheptadine and methysergide, and one acetylcholine (Ach) antagonist, atropine, did not effect morphine or LSD discrimination. The narcotic antagonist, naloxone, blocked the stimulus effect of morphine, but did not alter LSD discrimination. These results indicate that the morphine and LSD stimuli are dissimilar and that the integrity of 5-HT or Ach nervous systems is not essential for morphine or LSD to serve as a discriminative stimulus. 相似文献
18.
19.
P. Blanckaert I. Burvenich F. Devos G. Slegers 《Journal of labelled compounds & radiopharmaceuticals》2007,50(3):183-188
This work reports the synthesis, radiolabelling and in vivo evaluation in NMRI mice of [123I]‐(4‐fluorophenyl)[1‐(3‐iodophenethyl)piperidin‐4‐yl]methanone ([123I]‐3‐I‐CO) as a potential SPECT tracer for the 5‐HT2A receptor. The tributylstannylprecursor was synthesized with a 15% overall yield. Radiolabelling was performed using an electrophilic iododestannylation with yields of 85%. Radiochemical purity was always >95%. Log P was determined to be 3.10±0.10. The tracer showed good uptake in mouse brain (6.3±1.3% ID/g tissue at 10 min p.i., 2±0.36% ID/g tissue at 1 h p.i.). These results warrant further research in larger animals to determine suitability of [123I]‐3‐I‐CO as a 5‐HT2A tracer. Copyright © 2007 John Wiley & Sons, Ltd. 相似文献
20.
Test purchase,identification and synthesis of 2‐amino‐1‐(4‐bromo‐2, 5‐dimethoxyphenyl)ethan‐1‐one (bk‐2C‐B) 下载免费PDF全文
John D. Power Pierce Kavanagh John O'Brien Michael Barry Brendan Twamley Brian Talbot Geraldine Dowling Simon D. Brandt 《Drug testing and analysis》2015,7(6):512-518
2‐Amino‐1‐(4‐bromo‐2,5‐dimethoxyphenyl)ethan‐1‐one (bk‐2C‐B) has been recently offered for purchase by a variety of Internet retailers. This substance may be considered a cathinone analogue of the phenethylamine 2‐(4‐bromo‐2,5‐dimethoxyphenyl)ethan‐1‐amine (2C‐B) which suggests that it may have psychoactive effects in humans. A test purchase of bk‐2C‐B was carried out and its identity was confirmed by a range of analytical techniques including nuclear magnetic resonance spectroscopy, gas and liquid chromatography, and high‐resolution mass spectrometry. Confirmation was also obtained from the synthesis of bk‐2C‐B based on the implementation of the Delépine reaction in which the α‐brominated intermediate was reacted with hexamethylenetetramine to afford the primary amine. Analysis of underivatized bk‐2C‐B by gas chromatography–mass spectrometry (GC‐MS) showed that there was potential for artificial formation of 1‐(4‐bromo‐2,5‐dimethoxyphenyl)ethanone and a pyrazine dimer, these substances were not detected when employing liquid chromatographic analysis. Ion chromatography and X‐ray crystallography analysis confirmed that the purchased bk‐2C‐B consisted of a hydrochloride and hydrobromide salt mixture, which indicated that it might have been prepared by the hexamethylenetetramine route followed by hydrochloric acid hydrolysis of the quaternary ammonium salt. X‐ray crystallography also revealed that the purchased (mixed HCl/HBr salt) and synthesized bk‐2C‐B (HCl salt) exists as polymorphs. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献