NMDA receptor affinities of 1,2-diphenylethylamine and 1-(1,2-diphenylethyl)piperidine enantiomers and of related compounds.
TL;DR: The synthesis of the dicyclohexyl analogues of DPEA and related compounds were tested as inhibitors of [(3)H]MK-801 binding to rat brain membranes and exhibited stereospecific sensitivity to the modulator spermine.
About: This article is published in Bioorganic & Medicinal Chemistry.The article was published on 2009-05-01. It has received 34 citations till now. The article focuses on the topics: Channel blocker.
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TL;DR: The adverse effects noted in analytically confirmed cases of NPS intoxication involving diphenidine or MXP were similar to those reported for other dissociative substances such as ketamine and methoxetamine, but the high proportion of polysubstance use might have played a role in the intoxication and clinical features in some cases.
Abstract: Background. Diphenidine (1-(1,2-diphenylethyl)piperidine) and its 2-methoxylated derivative methoxphenidine (MXP, 2-MeO-diphenidine) are substances with dissociative effects that were recently introduced for “recreational” purpose through the online-based sale of new psychoactive substances (NPS). A number of analytically confirmed non-fatal intoxications associated with diphenidine or MXP have occurred in Sweden and were included in the STRIDA project. Study design. Observational case series of consecutive patients with admitted or suspected intake of NPS and requiring intensive treatment in an emergency room and hospitalization in Sweden. Patients and methods. Blood and urine samples were collected from intoxicated patients presenting at emergency departments all over the country. NPS analysis was performed by multi-component liquid chromatography–mass spectrometry methods. Data on clinical features were collected during telephone consultations with the Poisons Information Centre and retrieved f...
72 citations
TL;DR: Clinical and bioanalytical data from analytically confirmed non-fatal intoxications associated with 3- and/or 4-MeO-PCP within the STRIDA project constitute an important basis for the assessment of NPS hazard and availability.
Abstract: Background. 3-Methoxy-phencyclidine (3-MeO-PCP) and 4-methoxy-phencyclidine (4-MeO-PCP) are analogs of and drug substitutes for the dissociative substance PCP (“Angel dust”), a recreational drug that was most popular in the 1970s. In Sweden, use of methoxylated PCP analogs was noted starting in mid-2013, according to statistics from the Poisons Information Centre. The objective of this case series was to present clinical and bioanalytical data from analytically confirmed non-fatal intoxications associated with 3-MeO-PCP and/or 4-MeO-PCP within the STRIDA project. Study design. Observational case series of consecutive patients with self-reported or suspected exposure to new psychoactive substances (NPS) and who require hospital care. Patients and methods. Blood and urine samples were collected from intoxicated patients presenting at emergency departments (ED) or intensive care units (ICU) all over Sweden. NPS analysis was performed by multicomponent liquid chromatographic–tandem mass spectrometric (LC–MS/M...
52 citations
TL;DR: The results suggest that these 1,2-diarylethylamines are relatively selective NMDAR antagonists with weak off-target inhibitory effects on dopamine and norepinephrine reuptake.
Abstract: 1,2-Diarylethylamines including lanicemine, lefetamine, and remacemide have clinical relevance in a range of therapeutic areas including pain management, epilepsy, neurodegenerative disease and depression. More recently 1,2-diarylethylamines have been sold as ‘legal highs’ in a number of different forms including powders and tablets. These compounds are sold to circumvent governmental legislation regulating psychoactive drugs. Examples include the opioid MT-45 and the dissociative agents diphenidine (DPH) and 2-methoxy-diphenidine (2-MXP). A number of fatal and non-fatal overdoses have been linked to abuse of these compounds. As with many ‘legal highs’, little is known about their pharmacology. To obtain a better understanding, the effects of DPH, 2-MXP and its 3- and 4-MeO- isomers, and 2-Cl-diphenidine (2-Cl-DPH) were investigated using binding studies at 46 central nervous system receptors including the N-methyl-D-aspartate receptor (NMDAR), serotonin, dopamine, norepinephrine, histamine, and sigma receptors as well as the reuptake transporters for serotonin, dopamine and norepinephrine. Reuptake inhibition potencies were measured at serotonin, norepinephrine and dopamine transporters. NMDAR antagonism was established in vitro using NMDAR-induced field excitatory postsynaptic potential (fEPSP) experiments. Finally, DPH and 2-MXP were investigated using tests of pre-pulse inhibition of startle (PPI) in rats to determine whether they reduce sensorimotor gating, an effect observed with known dissociative drugs such as phencyclidine (PCP) and ketamine. The results suggest that these 1,2-diarylethylamines are relatively selective NMDAR antagonists with weak off-target inhibitory effects on dopamine and norepinephrine reuptake. DPH and 2-MXP significantly inhibited PPI. DPH showed greater potency than 2-MXP, acting with a median effective dose (ED50) of 9.5 mg/kg, which is less potent than values reported for other commonly abused dissociative drugs such as PCP and ketamine.
51 citations
Cites background or methods from "NMDA receptor affinities of 1,2-dip..."
..., the two DPH enantiomers showed lower affinity than that reported both here and by Gray and Cheng ((S-)-DPH 120 nM, (R)-DPH 5,250 nM) [18]....
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...used [(3)H]-MK-801 to label NMDAR from a different tissue source (whole cell membranes prepared from rat cortex and hippocampus) than the current study (rat forebrain homogenate) [18]....
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...Aside from some NMDAR binding studies [17, 18] and a recent publication about the metabolism of DPH [19], little information has been published regarding the pharmacology of the dissociative ‘research chemicals’DPH and 2-MXP....
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TL;DR: Three deaths which involved the detection of 2-MXP in post-mortem blood and urine were encountered in forensic casework and analytical data is presented to assist analytical toxicologists with future casework.
Abstract: 2-Methoxydiphenidine, i.e. 1-[1-(2-methoxyphenyl)-2-phenylethyl]piperidine, also known as 'MXP' or '2-MeO-diphenidine' (or 2-MXP), has been available as a 'research chemical' since 2013 as a purported alternative to the 'dissociative anesthetics' methoxetamine and ketamine. Three deaths which involved the detection of 2-MXP in post-mortem blood and urine were encountered in forensic casework. The 2-, 3- and 4-methoxyphenyl positional isomers were synthesized to confirm the identity and concentration of 2-MXP. The 2-MXP femoral blood concentrations in the cases were found to be 24.0, 2.0 and 1.36 mg/L (the latter with an alternative cause of death). Some additional prescription drugs were encountered at therapeutic concentrations in all three cases. Analysis of the biofluids allowed the detection and characterization of various metabolites, including the suggested presence of hydroxy-2-MXP as the main metabolite with the hydroxyl group located on the piperidine rather than the phenyl or benzyl moiety. Additional metabolites included O-desmethyl-2-MXP and hydroxylated O-desmethyl-2-MXP. Diphenidine and hydroxy-diphenidine, also showing the presence of the hydroxyl group on the piperidine ring, were also detected. It was not possible to identify whether these arose from 2-MXP biotransformation or whether they represented the presence of diphenidine as a separate substance. These are the first published fatalities involving 2-MXP and presents analytical data to assist analytical toxicologists with future casework.
45 citations
Cites result from "NMDA receptor affinities of 1,2-dip..."
...comparisons with what has been described for diphenidine, MXE and ketamine (1, 4, 9, 19, 23)....
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TL;DR: It is demonstrated that the monoamine transporter inhibition and receptor interactions most likely mediate the psychoactive effects of diclofensine and possibly play a contributory role for diphenidine and methoxphenidine.
35 citations
Cites background from "NMDA receptor affinities of 1,2-dip..."
...Diphenidine and methoxphenidine act as N-methylD-aspartate receptor antagonists (Berger et al., 2009; Wallach et al., 2015), and their effects have been described as being comparable to other dissociative anesthetic drugs, such as ketamine (Helander et al....
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...Diphenidine and methoxphenidine act as N-methylD-aspartate receptor antagonists (Berger et al., 2009; Wallach et al., 2015), and their effects have been described as being comparable to other dissociative anesthetic drugs, such as ketamine (Helander et al., 2015; Morris and Wallach, 2014)....
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References
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28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: The analysis described shows K I does not equal I 50 when competitive inhibition kinetics apply; however, K I is equal to I 50 under conditions of either noncompetitive or uncompetitive kinetics.
12,583 citations
TL;DR: In this article, a reagent formed by combining diethyl azodicarboxylate (DEAD) and triphenylphosphine (TPP) could be utilized in the intermolecular dehydration between an alcohol and various acidic components such as carboxylic acids, phosphoric diesters, imides, and active methylene compounds.
Abstract: The reagent formed by combining diethyl azodicarboxylate (DEAD) and triphenylphosphine (TPP) could be utilized in the intermolecular dehydration between an alcohol and various acidic components such as carboxylic acids, phosphoric diesters, imides, and active methylene compounds. By the use of DEAD and TPP, diols and hydroxy acids gave cyclic ethers and lactones, respectively. The reaction of nucleosides with DEAD and TPP afforded triphenylphosphoranylnucleosides. Alcohols reacted with 2,6-di-t-butyl-4-nitrophenol in the presence of DEAD and TPP to give aci-nitroesters which converted into the corresponding carbonyl compounds.
3,209 citations
TL;DR: In this paper, the application of (S)-1,10-binaphthyl-2,20-diol as NMR chiral solvating agent (CSA) for omeprazole, and three of its analogs (lanso-, panto-, and rabe-prazole) was investigated.
Abstract: The application of (S)-1,10-binaphthyl-2,20-diol as NMR chiral solvating agent (CSA) for omeprazole, and three of its analogs (lanso-, panto-, and rabe-prazole) was investigated. The formation of diastereomeric host–guest complexes in solution between the CSA and the racemic substrates produced sufficient NMR signal splitting for the determination of enantiomeric excesses by Hor F-NMR spectroscopy. Using of hydrophobic deuterated solvents was mandatory for obtaining good enantiodiscrimination, thus suggesting the importance of intermolecular hydrogen bonds in the stabilization of the complexes. The method was applied to the fast quantification of the enantiomeric purity of in-process samples of S-omeprazole. Chirality 00:000–000, 2009. VC 2009
885 citations