- Enrichment of arachidonic acid for the enzymatic synthesis of arachidonoyl ethanolamide
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Arachidonoyl ethanolamide is an endogenous cannabinoid neurotransmitter that potentially has therapeutic properties. In this study, we report an enzymatic method to synthesize this bioactive ethanolamide. First, free fatty acids were obtained from arachidonic acid-rich oil and then arachidonic acid was enriched by urea inclusion and AgNO3 solution fractionation. Arachidonic acid content was increased from 40.2 to 78.4 % with 27.6 ± 1.8 % total fatty acid mass yield (w/w, relative to total free fatty acid) after urea inclusion. Purification of arachidonic acid by AgNO3 solution fractionation was optimized, and under the optimal conditions, a product with 90.7 % arachidonic acid was obtained with 80.4 % mass yield (w/w, relative to total free fatty acid). Finally, arachidonoyl ethanolamide was synthesized by reacting the purified arachidonic acid with ethanolamine in hexane using Novozym 435 lipase of Novozymes America (Blair, NE), which resulted in the formation of 88.4 ± 0.6 % arachidonoyl ethanolamide with 72.7 ± 2.2 % mass yield. The main novelties of this study are the enrichment of polyunsaturated fatty acids by AgNO3 solution fractionation which has received little attention in recent years, and this is the first time the synthesis of arachidonoyl ethanolamide is reported.
- Wang, Xingguo,Wang, Xiaosan,Wang, Tong
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- Methyl arachidonyl fluorophosphonate: A potent irreversible inhibitor of anandamide amidase
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Anandamide amidase (EC 3.5.1.4) is responsible for the hydrolysis of arachidonoyl ethanolamide (anandamide). Relatively selective and potent enzyme reversible inhibitors effective in the low micromolar range, such as arachidonyl trifluoromethyl ketone (Arach-CF3), have been described (Koutek et al., J Biol Chem 269: 22937-22940, 1994). In the current study, methyl arachidonyl fluorophosphonate (MAFP), an arachidonyl binding site directed phosphonylation reagent, was tested as an inhibitor of anandamide amidase and as a ligand for the CB1 cannabinoid receptor. MAFP was 800 times more potent than Arach-CF3 and phenylmethylsulfonyl fluoride (PMSF) as an amidase inhibitor in rat brain homogenates. In intact neuroblastoma cells, MAFP was also approximately 1000-fold more potent than Arach-CF3. MAFP demonstrated selectivity towards anandamide amidase for which it was approximately 3000 and 30,000-fold more potent than it was towards chymotrypsin and trypsin, respectively. MAFP displaced [3H]CP-55940 binding to the CB1 cannabinoid receptor with an IC50 of 20 nM vs 40 nM for anandamide. It bound irreversibly and prevented subsequent binding of the cannabinoid radioligand [3H]CP-55940 at that locus. These studies suggest that MAFP is a potent and specific inhibitor of anandamide amidase and, in addition, can interact with the cannabinoid receptors at the cannabinoid binding site. This is the first report of a potent and relatively selective irreversible inhibitor of arachidonoyl ethanolamide amidase.
- Deutsch, Dale G.,Omeir, Romelda,Arreaza, Gladys,Salehani, David,Prestwich, Glenn D.,Huang, Zheng,Howlett, Allyn
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- ANANDAMIDE COMPOUNDS
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The present application provides anandamide and 2-arachidonyl glycerol compounds useful for treating a disease or disorder in a subject in need thereof. Pharmaceutical compositions comprising the compounds and methods of treating diseases or disorders are also provided.
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(2020/07/25)
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- COMPOSITIONS HAVING AN AGENT AND AN ENHANCER THEREOF, METHODS OF USE, AND DELIVERY SYSTEMS
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The present invention relates to compositions, and methods of use thereof, related to the endocannabinoid system and includes therapeutic compositions including an agent and an enhancer thereof, optionally, formulated for administration of the therapeutic compositions, preferably in a measured amount.
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- A Convenient Protocol for the Synthesis of Fatty Acid Amides
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Several classes of biologically occurring fatty acid amides have been reported from mammalian and plant sources. Many amides conjugated with fatty acids of mammalian origin exhibit specific activation of individual receptors. Their potential as pharmacological tools or as lead compounds towards the development of novel therapeutics is of great interest. Hence, access to such amides by a practical, high-yielding and scalable protocol without affecting the geometry or position of sensitive functionalities is needed. A protocol that meets all these requirements involves activation of the corresponding acid with carbonyl diimidazole (CDI) followed by reaction with the desired amine or its hydrochloride. More than fifty compounds have been prepared in generally high yields.
- Johansson, Silje J. R.,Johannessen, Tonje,Ellefsen, Christiane F.,Ristun, Mali S.,Antonsen, Simen,Hansen, Trond V.,Stenstrom, Yngve,Nolsoe, Jens M. J.
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supporting information
p. 213 - 217
(2019/01/14)
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- INHIBITORS OF N-ACYLPHOSPHATIDYLETHANOLAMINE PHOSPHOLIPASE D (NAPE-PLD)
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The invention relates to a compound of the formula (I) as novel inhibitor of N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD), and to use thereof for the prophylaxis or treatment of diseases associated with NAPE-PLD. wherein in a ring A, X1 is N, or CR4; X2 is N or CR5; X3 is N or CH; with the proviso that at least one of X1 and X3 is N.
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- Protective role of the novel hybrid 3,5-dipalmitoyl-nifedipine in a cardiomyoblast culture subjected to simulated ischemia/reperfusion
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This work investigated the acute effects of the calcium channel blocker nifedipine and its new fatty hybrid derived from palmitic acid, 3,5-dipalmitoyl-nifedipine, compared to endocannabinoid anandamide during the process of inducing ischemia and reperfusion in cardiomyoblast H9c2 heart cells. The cardiomyoblasts were treated in 24 or 96-well plates (according to the test being performed) and maintaining the treatment until the end of hypoxia induction. The molecules were tested at concentrations of 10 and 100?μM, cells were treated 24?h after assembling the experimental plates and immediately before the I/R. Cell viability, apoptosis and necrosis, and generation of reactive oxygen species were evaluated. Nifedipine and 3,5-dipalmitoyl-nifedipine were used to assess radical scavenging potential and metal chelation. All tested molecules managed to reduce the levels of reactive oxygen species compared to the starvation?+?vehicle group. In in vitro assays, 3,5-dipalmitoyl-nifedipine showed more antioxidant activity than nifedipine. These results indicate the ability of this molecule to act as a powerful ROS scavenger. Cell viability was highest when cells were induced to I/R by both concentrations of anandamide and the higher concentration of DPN. These treatments also reduced cell death. Therefore, it was demonstrated that the process of hybridization of nifedipine with two palmitic acid chains assigns a greater cardioprotective effect to this molecule, thereby reducing the damage caused by hypoxia and reoxygenation in cardiomyoblast cultures.
- Santa-Helena, Eduarda,Teixeira, Stefanie,Castro, Micheli Rosa de,Cabrera, Diego da Costa,D'Oca, Caroline Da Ros Montes,D'Oca, Marcelo G. Montes,Votto, Ana Paula S.,Nery, Luiz Eduardo Maia,Gon?alves, Carla Amorim Neves
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p. 356 - 364
(2017/05/31)
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- Involvement of reactive oxygen species in the oleoylethanolamide effects and its pyrazonilic analogue in melanoma cells
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The search for more substances that effectively fight melanoma is extremely important, because of its aggressive nature. In this sense, the molecular hybridization is a promising strategy. The aim of this work is to evaluate whether the antiproliferative effect of the endocannabinoid oleoylethanolamide can be improved with the addition of a trifluoromethylated pyrazolinic nucleus on its structure in B16F10 cell line. The pyrazolinic analog was named oleoyl pyrazoline. We also compared the effects of oleoylethanolamide and that of the classic endocannabinoid anandamide (AEA). The cell viability was evaluated by MTT assay, the intracellular reactive oxygen species generation by fluorimetry, and apoptosis/necrosis by fluorescent microscopy. Also, α-tocopherol antioxidant was used to evaluate the involvement of reactive oxygen species in the cellular response. Although the effects of AEA occur in smaller concentrations, the results show that the effects of AEA and oleoylethanolamide were similar. The results showed a decrease in cell viability, induction of apoptosis and necrosis, and increased generation of reactive oxygen species by the oleoylethanolamide, while the oleoyl pyrazoline increased cell proliferation and decreased reactive oxygen species. Additionally, the effects of oleoylethanolamide in cell viability were decreased by inhibiting the generation of reactive oxygen species by α-tocopherol. Therefore, it is possible to suggest the involvement of reactive oxygen species in the effect of oleoylethanolamide in the B16F10 cells. Considering the great need to find substances that can fight melanoma and the lack of greater elucidation in the action mechanisms of cannabinoids and their analogs, this work provides important new information that could serve as reference to other studies.
- Antiqueira-Santos, Priscila,dos Santos, Daiane S.,Hack, Carolina R. L.,Flores, Alex Fabiani C.,Montes D’Oca, Marcelo G.,Piovesan, Luciana A.,Nery, Luiz Eduardo M.,Votto, Ana Paula S.
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p. 2727 - 2736
(2017/10/06)
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- Improved enzymatic procedure for the synthesis of anandamide and N-fatty acylalkanolamine analogues: A combination strategy to antitumor activity
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Twenty N-fatty acylamines from linolenic and arachidonic acids, fifteen of them new compounds, were obtained through Candida antarctica B lipase-catalyzed esterification and aminolysis reactions in very good yields and with high chemoselectivity. The optimal reaction conditions were achieved by studying the reaction parameters (temperature, E/S ratio, alcohol and alkanolamine/fatty acid ratio, time, solvent, free-solvent system, etc.). To identify ideal enzymatic methods for generating the alkanolamides we evaluated enzyme performance in three procedures: i) aminolysis of ethyl ester, ii) direct condensation between the fatty acid and the alkanolamine, and iii) a one-pot/two-step conversion of fatty acids into alkanolamides via in situ formation of the ethyl ester and subsequent aminolysis by the alkanolamine. The advantages noted with the enzymatic methodology, such as mild reaction conditions and low environmental impact, underscore biocatalysis as a convenient way to prepare the reported compounds. The cytotoxic activities of all compounds and mixtures of anandamide and its analogues were evaluated in rat glioma C6 cells. These studies reveal that some anandamide analogues enhance the antitumor effects of anandamide, suggesting their possible application as therapeutic tools in cancer treatment. Twenty N-fatty acylamines from linolenic and arachidonic acids were obtained by one-pot/two-step Candida antarctica B lipase-catalyzed esterification and aminolysis reactions in very good yields with high chemoselectivity. Cytotoxicity assays using rat glioma C6 cells revealed that some analogues enhanced the antitumor effects of anandamide (AEA), suggesting possible anticancer applications.
- Quintana, Paula G.,Garca Liares, Guadalupe,Chanquia, Santiago N.,Gorojod, Roxana M.,Kotler, Mnica L.,Baldessari, Alicia
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p. 518 - 528
(2016/02/18)
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- Synthesis and evaluation of fatty acid amides on the N-oleoylethanolamide-like activation of peroxisome proliferator activated receptor α
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A series of fatty acid amides were synthesized and their peroxisome proliferator-activated receptor α (PPAR-α) agonistic activities were evaluated in a normal rat liver cell line, clone 9. The mRNAs of the PPAR-α downstream genes, carnitine-palmitoyltransferase-1 and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) as PPAR-α agonistic activities. We prepared nine oleic acid amides. Their PPAR-α agonistic activities were, in decreasing order, N-oleoylhistamine (OLHA), N-oleoylglycine, Oleamide, N-oleoyltyramine, N-oleoylsertonin, and Olvanil. The highest activity was found with OLHA. We prepared and evaluated nine N-acylhistamines (N-acyl-HAs). Of these, OLHA, C16:0-HA, and C18:1Δ9-trans-HA showed similar activity. Activity due to the different chain length of the saturated fatty acid peaked at C16:0-HA. The PPAR-α antagonist, GW6471, inhibited the induction of the PPAR-α downstream genes by OLHA and N-oleoylethanolamide (OEA). These data suggest that N-acyl-HAs could be considered new PPAR-α agonists.
- Takao, Koichi,Noguchi, Kaori,Hashimoto, Yosuke,Shirahata, Akira,Sugita, Yoshiaki
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p. 278 - 285
(2015/04/22)
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- Optimized synthesis and characterization of N-acylethanolamines and O-acylethanolamines, important family of lipid-signalling molecules
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The endocannabinoid anandamide (N-arachidonoylethanolamine, AEA), a physiologically occurring bioactive compound on CB1 and CB2 receptors, has multiple physiological functions. Since the discovery of AEA additional non-cannabinoid endogenous compounds such as N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA) have been identified from mammalian tissues. Virodhamine (O-arachidonoylethanolamine, VA) is the only identified new member of the endocannabinoid family that is characterised by an ester linkage between acylic acid and ethanolamine instead of the amide linkage found in AEA and others non-cannabinoid N-acylethanolamines. It has been reported, as a cautionary note for lipid analyses, that VA can be produced nonenzymatically from AEA (and vice versa) as consequence of O,N-acyl migrations. O,N-acyl migrations are well documented in synthetic organic chemistry literature, but are not well described or recognized with regard to methods in lipid isolation or lipid enzyme studies. We here report an economical and effective protocol for large scale synthesis and characterization of some N- and O-acylethanolamines that could be useful as reference standards in order to investigate their possible formation in biological membranes, with potentially interesting biological properties.
- Ottria, Roberta,Casati, Silvana,Ciuffreda, Pierangela
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p. 705 - 711
(2013/01/15)
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- Synthesis, in vitro and in vivo evaluation, and radiolabeling of aryl anandamide analogues as candidate radioligands for in vivo imaging of fatty acid amide hydrolase in the brain
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Fatty acid amide hydrolyase (FAAH) is one of the main enzymes responsible for terminating the signaling of endocannabinoids in the brain. Imaging FAAH in vivo using PET or SPECT is important to deeper understanding of its role in neuropsychiatric disorders. However, at present, no radioligand is available for mapping the enzyme in vivo. Here, we synthesized 18 aryl analogues of anandamide, FAAH's endogenous substrate, and in vitro evaluated their potential as metabolic trapping tracers. Interaction studies with recombinant FAAH revealed good to very good interaction of the methoxy substituted aryl anandamide analogues 17, 18, 19, and 20 with FAAH and they were identified as competing substrates. Compounds 17 and 18 did not display significant binding to CB1 and CB2 cannabinoid receptors and stand out as potential candidate metabolic trapping tracers. They were successfully labeled with 11C in good yields and high radiochemical purity and displayed brain uptake in C57BL/6J mice. Radioligands [11C]-17 and [ 11C]-18 merit further investigation in vivo.
- Wyffels, Leonie,Muccioli, Giulio G.,De Bruyne, Sylvie,Moerman, Lieselotte,Sambre, Johan,Lambert, Didier M.,De Vos, Filip
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supporting information; experimental part
p. 4613 - 4622
(2010/02/28)
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- Radiosynthesis, in vitro and in vivo evaluation of 123I-labeled anandamide analogues for mapping brain FAAH
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Fatty acid amide hydrolase (FAAH) is one of the main enzymes responsible for terminating the signaling of endocannabinoids, including anandamide. This paper is the first report of the synthesis, [123I]-labeling and in vitro and in vivo evaluation of anandamide analogues as potential metabolic trapping radioligands for in vivo evaluation of brain FAAH. N-(2-Iodoethyl)linoleoylamide (2) and N-(2-iodoethyl)arachidonylamide (4) were synthesized with good yields (75% and 86%, respectively) in a two steps procedure starting from their respective acids. In vitro analyses, performed using recombinant rat FAAH and [3H]-anandamide, demonstrated interaction of 2 and 4 with FAAH (IC50 values of 5.78 μM and 3.14 μM, respectively). [123I]-2 and [123I]-4 were synthesized with radiochemical yields of 21% and 12%, respectively, and radiochemical purities were >90%. Biodistribution studies in mice demonstrated brain uptake for both tracers (maximum values of 1.23%ID/g at 3 min pi for [123I]-2 and 0.58%ID/g at 10 min pi for [123I]-4). However, stability studies demonstrated the sensitivity of both tracers to dehalogenation.
- wyffels, Leonie,De Bruyne, Sylvie,Blanckaert, Peter,Lambert, Didier M.,De Vos, Filip
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experimental part
p. 49 - 56
(2011/02/25)
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- Synthesis of all-trans anandamide: A substrate for fatty acid amide hydrolase with dual effects on rabbit platelet activation
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Anandamide (AEA) presents the four double bonds in the cis configuration, deriving from the arachidonic acid moiety. In the context of an antisense strategy based on the double bond configuration, all-trans AEA (t-AEA) was synthesized in high yield starting from all-trans methyl arachidonate and ethanolamine in the presence of KCN. t-AEA was assayed on rabbit platelet aggregation, obtaining effect only at high concentrations (>10-4 M) after an also concentration-dependent lag phase. At lower concentrations it inhibited PAF-induced rabbit platelet aggregation with an IC50 = 4.6 × 10-6 M. In contrast to anandamide, the activation of platelets was not due to the conversion of t-AEA to trans arachidonic acid, as ascertained by negative results with FAAH inhibitors. However, t-AEA was found to be a substrate for fatty acid amide hydrolase (FAAH), the enzyme that cleaves anandamide and regulates in vivo the magnitude and duration of the signaling induced by this lipid messenger.
- Ferreri, Carla,Anagnostopoulos, Dimitris,Lykakis, Ioannis N.,Chatgilialoglu, Chryssostomos,Siafaka-Kapadai, Athanassia
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experimental part
p. 8359 - 8365
(2009/04/11)
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- A spectrophotometric assay for fatty acid amide hydrolase suitable for high-throughput screening
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Signalling via the endocannabinoids anandamide and 2-arachidonylglycerol appears to be terminated largely through the action of the enzyme fatty acid amide hydrolase (FAAH). In this report, we describe a simple spectrophotometric assay to detect FAAH activity in vitro using the ability of the enzyme to hydrolyze oleamide and measuring the resultant production of ammonia with a NADH/NAD+-coupled enzyme reaction. This dual-enzyme assay was used to determine Km and Vmax values of 104 μM and 5.7 nmol/min/mg protein, respectively, for rat liver FAAH-catalyzed oleamide hydrolysis. Inhibitor potency was determined with the resultant rank order of methyl arachidonyl fluorophosphonate > phenylmethylsulphonyl fluoride > anandamide. This assay system was also adapted for use in microtiter plates and its ability to detect a known inhibitor of FAAH demonstrated, highlighting its potential for use in high-throughput screening.
- De Bank, Paul A.,Kendall, David A.,Alexander, Stephen P.H.
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p. 1187 - 1193
(2007/10/03)
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- 9,11-cycloendoperoxide pro-drugs of prostaglandin analogues for treatment of ocular hypertension and glaucoma
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9,11-Cycloendoperoxide derivatives of biologically active prostaglandin analogs, and particularly of the ocular hypotensive drugs Bimatoprost, Latanaprost, Unoprostone, Travoprost and prostaglandin H2 1-ethanolamide or of structurally closely related analogs, are pro-drugs which hydrolyze under physiological conditions to provide prostaglandin analogues that are capable of providing sustained ocular and other in vivo concentrations of the respective drugs. The compounds of the invention have the formula shown below where the variables have the meaning defined in the specification.
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(2010/11/30)
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- Solid-phase synthesis of anandamide analogues
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The endocannabinoids are amides and esters of arachidonic acid that can mimic the pharmacological properties of Δ9-tetrahydrocannabinol (Δ9-THC). Anandamide, the most prominent of the endocannabinoids, has been implicated in both metabolic/physiological roles of the central nervous system, making it an attractive medicinal target. As such, we report the first solid-phase methodology that expedites access to various anandamide analogues. Our synthesis features a repetitive Cu-mediated coupling reaction between terminal alkynes and propargyl halides or allylic halides.
- Qi, Longwu,Meijler, Michael M.,Lee, Sang-Hyeup,Sun, Chengzao,Janda, Kim D.
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p. 1673 - 1675
(2007/10/03)
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- Elevated circulating levels of anandamide after administration of the transport inhibitor, AM404
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The biological actions of the endogenous cannabinoid anandamide are terminated by carrier-mediated transport into neurons and astrocytes, followed by enzymatic hydrolysis. Anandamide transport is inhibited by the compound N-(4-hydroxyphenyl)arachidonylamide (AM404). AM404 potentiates several responses elicited by administration of exogenous anandamide, suggesting that it may also protect endogenous anandamide from inactivation. To test this hypothesis, we studied the effects of AM404 on the plasma levels of anandamide using high-performance liquid chromatography/mass spectrometry (HPLC/MS). Systemic administration of AM404 (10 mg kg-1 intraperitoneal, i.p.) caused a gradual increase of anandamide in rat plasma, which was significantly different from untreated controls at 60 and 120 min after drug injection. In plasma, both AM404 and anandamide were associated with a plasma protein, which we identified as albumin by non-denaturing polyacrylamide gel electrophoresis. AM404 (10 mg kg-1, i.p.) caused a time-dependent decrease of motor activity, which was reversed by the cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide·hydrochloride (SR141716A, 0.5 mg kg-1, i.p). These results are consistent with the hypothesis that AM404 inhibits anandamide inactivation in vivo. (C) 2000 Elsevier Science B.V.
- Giuffrida, Andrea,Rodriguez De Fonseca, Fernando,Nava, Felice,Loubet-Lescoulie, Patrick,Piomelli, Daniele
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p. 161 - 168
(2007/10/03)
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- Arachidonic acid amide inhibitors of gap junction cell-cell communication
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A series of arachidonic acid amides including anandamide and arachidonamide that act as potent inhibitors of the rat glial cell gap junction is described.
- Boger, Dale L.,Sato, Haruhiko,Lerner, Aaron E.,Guan, Xiaojun,Gilula, Norton B.
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p. 1151 - 1154
(2007/10/03)
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- Use of N-acyl derivatives of aminoalcohols in the manufacture of a medicament for practicing neuroprotective action in neuropathological states connected with excitotoxicity
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The use of N-acyl derivatives of aminoalcohols with mono- and di-carboxylic acids for the prevention and treatment of diseases connected with hyper and prolonged excitation by excitatory amino acids is described.
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- Pharmacological and behavioral evaluation of alkylated anandamide analogs
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Anandamide (arachidonylethanolamide), isolated from porcine brain, has been shown to bind to the cannabinoid receptor and also to produce cannabimimetic activity in pharmacological assays. This study examined structure-activity relationships in alkylated anandamide analogs. The analogs were evaluated for their ability to displace [3H]CP-55,940 in a filtration binding assay using rat brain membranes in the presence and absence of the enzyme inhibitor phenylmethylsulfonyl fluoride (PMSF). Behavioral activity was assessed by the ability of the analogs to produce hypomotility and antinociception. Methylations at carbons 2 and 1' produced compounds stable in the absence of PMSF with similar affinities and behavioral activity as anandamide. Addition of larger alkyl groups at these positions or nitrogen methylation reduced receptor affinity and behavioral potency. These results indicate that methylations at specific carbons of anandamide confer stability in vitro.
- Adams, Irma B.,Ryan, William,Singer, Michael,Razdan, Raj K.,Compton, David R.,Martin, Billy R.
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p. 2041 - 2048
(2007/10/03)
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- (R)-methanandamide: A chiral novel anandamide possessing higher potency and metabolic stability
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Four chiral congeners of arachidonylethanolamide (anandamide) have been synthesized and evaluated for (a) their ability to bind to the cannabinoid receptor in rat forebrain membranes and (b) their pharmacological potency as measured by the compounds' ability to inhibit electrically-evoked contractions of the mouse vas deferens. The lead analog was also tested for its potency in vivo. Of the analogs tested, (R)-(+)-arachidonyl-1'-hydroxy- 2'-propylamide [(R)-methanandamide] exhibited the highest affinity for the cannabinoid receptor with a K(i) of 20 ± 1.6 nM, 4-fold lower than that of anandamide (K(i) = 78 ± 2 nM). Moreover, determination of the cannabinoid binding affinity in the presence and absence of the protease inhibitor phenylmethanesulfonyl fluoride (PMSF) revealed that (R)-methanandamide possesses a remarkable stability to aminopeptidase hydrolysis. Pharmacological studies on mouse isolated vasa deferentia demonstrated that all four analogs produce concentration-related inhibition of the twitch response and the order of potency is the same as the rank order of the affinities of these agonists for cannabinoid binding sites. Furthermore, experiments with mice have demonstrated that (R)-methanandamide also possesses cannabimimetric properties in vivo, as established by the four tests of hypothermia, hypokinesia, ring immobility, and antinociception.
- Abadji,Lin,Taha,Griffin,Stevenson,Pertwee,Makriyannis
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p. 1889 - 1893
(2007/10/02)
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