OMDM-1
(Synonyms: (S)Noleoyl Tyrosinol) 目录号 : GC41362
An inhibitor of AEA uptake
Cas No.:616884-62-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Numerous analogs of arachidonoyl ethanolamide potentiate its biological activity. This potentiation is ascribed either to inhibition of AEA reuptake into neurons or inhibition of fatty acid amide hydrolase (FAAH) within the neurons. OMDM-1 is an endocannabinoid analog specifically designed to be a potent and selective inhibitor of the cellular uptake of AEA. Structurally, OMDM-1 is the amide of (S)-tyrosinol with oleic acid . In RBL-2H3 cells, OMDM-1 inhibits the cellular uptake of tritiated AEA with an IC50 of 2.4 µM, with negligible effects on the CB1 receptor and VR1.
| Cas No. | 616884-62-9 | SDF | |
| 别名 | (S)Noleoyl Tyrosinol | ||
| Canonical SMILES | CCCCCCCC/C=C\CCCCCCCC(=O)N[C@H](CO)Cc1ccc(O)cc1 | ||
| 分子式 | C27H45NO3 | 分子量 | 431.7 |
| 溶解度 | Ethanol: 30 mg/ml,DMF: 30 mg/ml,DMSO: Miscible,DMSO:PBS (pH 7.2) (1:1): .5 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3164 mL | 11.5821 mL | 23.1642 mL |
| 5 mM | 0.4633 mL | 2.3164 mL | 4.6328 mL |
| 10 mM | 0.2316 mL | 1.1582 mL | 2.3164 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
In vivo pharmacological actions of two novel inhibitors of anandamide cellular uptake
Eur J Pharmacol 2004 Jan 26;484(2-3):249-57.PMID:14744610DOI:10.1016/j.ejphar.2003.11.027.
Two inhibitors of the cellular uptake of the endocannabinoid anandamide, (R)-N-oleoyl-(1'-hydroxybenzyl)-2'-ethanolamine and (S)-N-oleoyl-(1'-hydroxybenzyl)-2'-ethanolamine (OMDM-1 and OMDM-2, respectively), were recently synthesized, and their in vitro pharmacological activity described. Here we have assessed their activity in two typical pharmacological responses of cannabimimetic compounds. We first examined whether these compounds exert any effect per se on locomotion and pain perception in rats, and/or enhance the effects of anandamide on these two processes. We compared the effects of the novel compounds with those produced by a previously developed selective inhibitor, N-arachidonoyl-(2-methyl-4-hydroxyphenyl)amine (VDM-11). When assayed alone, OMDM-1 and OMDM-2 (1-10 mg/kg, i.p.) did not affect any of the five motor parameters under investigation, although the former compound exhibited a trend for the inhibition of ambulation, fast movements, and speed in rats. OMDM-2 and, to a lesser extent, VDM-11 (5 mg/kg, i.p.) enhanced the motor-inhibitory effects of a noneffective dose (2 mg/kg, i.p.) of anandamide, while OMDM-1 did not. In a typical test of acute analgesia, OMDM-2 and VDM-11 (1-10 mg/kg, i.p.), but not OMDM-1, significantly enhanced the time spent by rats on a "hot plate." However, the same compounds (5 mg/kg, i.p.) did not enhance the analgesic effect of a subeffective dose (2 mg/kg, i.p.) of anandamide, whereas OMDM-1 exerted a strong trend towards potentiation (P=0.06). We next explored the possible use of the two novel compounds in a pathological condition. Thus, we determined if, like other previously developed anandamide reuptake inhibitors, OMDM-1 and OMDM-2 inhibit spasticity in an animal model of multiple sclerosis-the chronic relapsing experimental allergic encephalomyelitis in mice. As previously shown with a higher dose of VDM-11, both novel compounds (5 mg/kg, i.v.) significantly reduced spasticity of the hindlimb in mice with chronic relapsing experimental allergic encephalomyelitis. We suggest that OMDM-1 and, particularly, OMDM-2 are useful pharmacological tools for the study of the (patho)physiological role of the anandamide cellular uptake process, and represent unique templates for the development of new antispastic drugs.
Novel selective and metabolically stable inhibitors of anandamide cellular uptake
Biochem Pharmacol 2003 May 1;65(9):1473-81.PMID:12732359DOI:10.1016/s0006-2952(03)00109-6.
Novel aromatic analogues of N-oleoylethanolamine and N-arachidonoylethanolamine (anandamide, AEA) were synthesized and, based on the capability of similar compounds to interact with proteins of the endocannabinoid and endovanilloid signaling systems, were tested on: (i) cannabinoid CB(1) and CB(2) receptors; (ii) vanilloid VR1 receptors; (iii) anandamide cellular uptake (ACU); and (iv) the fatty acid amide hydrolase (FAAH). The (R)- and, particularly, the (S)-1'-(4-hydroxybenzyl) derivatives of N-oleoylethanolamine and AEA (OMDM-1, OMDM-2, OMDM-3, and OMDM-4) inhibited to a varied extent ACU in RBL-2H3 cells (K(i) ranging between 2.4 and 17.7 micro M), the oleoyl analogues (OMDM-1 and OMDM-2, K(i) 2.4 and 3.0 micro M, respectively) being 6- to 7-fold more potent than the arachidonoyl analogues (OMDM-3 and OMDM-4). These four compounds exhibited: (i) poor affinity for either CB(1) (K(i)> or = 5 micro M) or CB(2) (K(i)>10 micro M) receptors in rat brain and spleen membranes, respectively; (ii) almost no activity at vanilloid receptors in the intracellular calcium assay carried out with intact cells over-expressing the human VR1 (EC(50)> or = 10 micro M); and (iii) no activity as inhibitors of FAAH in N18TG2 cell membranes (K(i)>50 micro M). The oleoyl- and arachidonoyl-N'-(4-hydroxy-3-methoxybenzyl)hydrazines (OMDM-5 and OMDM-6), inhibited ACU (K(i) 4.8 and 7.0 micro M, respectively), and were more potent as VR1 agonists (EC(50) 75 and 50nM, respectively), weakly active as CB(1) receptor ligands (K(i) 4.9 and 3.2 micro M, respectively), and inactive as CB(2) ligands (K(i)>5 micro M) as well as on FAAH (K(i)> or = 40 micro M). In conclusion, we report two novel potent and selective inhibitors of ACU (OMDM-1 and OMDM-2) and one "hybrid" agonist of CB(1) and VR1 receptors (OMDM-6). Unlike other compounds of the same type, OMDM-1, OMDM-2, and OMDM-6 were very stable to enzymatic hydrolysis by rat brain homogenates.
Increased anandamide uptake by sensory neurons contributes to hyperalgesia in a model of cancer pain
Neurobiol Dis 2013 Oct;58:19-28.PMID:23644187DOI:10.1016/j.nbd.2013.04.018.
Opioids do not effectively manage pain in many patients with advanced cancer. Because anandamide (AEA) activation of cannabinoid type-1 receptors (CB1R) on nociceptors reduces nociception, manipulation of AEA metabolism in the periphery may be an effective alternative or adjuvant therapy in the management of cancer pain. AEA is hydrolyzed by the intracellular enzyme fatty acid amide hydrolase (FAAH), and this enzyme activity contributes to uptake of AEA into neurons and to reduction of AEA available to activate CB1R. We used an in vitro preparation of adult murine dorsal root ganglion (DRG) neurons co-cultured with fibrosarcoma cells to investigate how tumors alter the uptake of AEA into neurons. Evidence that the uptake of [(3)H]AEA into dissociated DRG cells in the co-culture model mimicked the increase in uptake that occurred in DRG cells from tumor-bearing mice supported the utility of the in vitro model to study AEA uptake. Results with the fluorescent AEA analog CAY10455 confirmed that an increase in uptake in the co-culture model occurred in neurons. One factor that contributed to the increase in [(3)H]AEA uptake was an increase in total cellular cholesterol in the cancer condition. Treatment with the FAAH inhibitor URB597 reduced CAY10455 uptake in the co-culture model to the level observed in DRG neurons maintained in the control condition (i.e., in the absence of fibrosarcoma cells), and this effect was paralleled by OMDM-1, an inhibitor of AEA uptake, at a concentration that had no effect on FAAH activity. Maximally effective concentrations of the two drugs together produced a greater reduction than was observed with each drug alone. Treatment with BMS309403, which competes for AEA binding to fatty acid binding protein-5, mimicked the effect of OMDM-1 in vitro. Local injection of OMDM-1 reduced hyperalgesia in vivo in mice with unilateral tumors in and around the calcaneous bone. Intraplantar injection of OMDM-1 (5μg) into the tumor-bearing paw reduced mechanical hyperalgesia through a CB1R-dependent mechanism and also reduced a spontaneous nocifensive behavior. The same dose reduced withdrawal responses evoked by suprathreshold mechanical stimuli in naive mice. These data support the conclusion that OMDM-1 inhibits AEA uptake by a mechanism that is independent of inhibition of FAAH and provide a rationale for the development of peripherally restricted drugs that decrease AEA uptake for the management of cancer pain.
A catalytically silent FAAH-1 variant drives anandamide transport in neurons
Nat Neurosci 2011 Nov 20;15(1):64-9.PMID:22101642DOI:10.1038/nn.2986.
The endocannabinoid anandamide is removed from the synaptic space by a selective transport system, expressed in neurons and astrocytes, that remains molecularly uncharacterized. Here we describe a partly cytosolic variant of the intracellular anandamide-degrading enzyme fatty acid amide hydrolase-1 (FAAH-1), termed FAAH-like anandamide transporter (FLAT), that lacked amidase activity but bound anandamide with low micromolar affinity and facilitated its translocation into cells. Known anandamide transport inhibitors, such as AM404 and OMDM-1, blocked these effects. We also identified a competitive antagonist of the interaction of anandamide with FLAT, the phthalazine derivative ARN272, that prevented anandamide internalization in vitro, interrupted anandamide deactivation in vivo and exerted profound analgesic effects in rodent models of nociceptive and inflammatory pain, which were mediated by CB(1) cannabinoid receptors. The results identify FLAT as a critical molecular component of anandamide transport in neural cells and a potential target for therapeutic drugs.
Selective inhibition of anandamide cellular uptake versus enzymatic hydrolysis--a difficult issue to handle
Eur J Pharmacol 2004 May 10;492(1):1-11.PMID:15145699DOI:10.1016/j.ejphar.2004.03.048.
There is considerable debate at present as to whether the uptake of anandamide (AEA) into cells is by a facilitated transport process or by passive diffusion driven by fatty acid amide hydrolase (FAAH). The possibility that both processes occur, but to different extents depending upon the cell type used, has been difficult to investigate pharmacologically since available compounds show little selectivity between inhibition of AEA uptake and inhibition of FAAH. Recently, three compounds, UCM707 [N-(Fur-3-ylmethyl)arachidonamide], OMDM-1 and OMDM-2 [the 1'-(S)- and 1'-(R)-enantiomers of the 1'-4-hydroxybenzoyl analogue of oleoylethanolamide], selective for the uptake process, have been described and we have used these compounds, together with AM404 [(N-(4-hydroxyphenyl) arachidonoyl amide)] and VDM11 [(5Z,8Z,11Z,14Z)-N-(4-Hydroxy-2-methylphenyl)-5,8,11,14-eicosatetraenamide]), with the initial aim of determining which mechanism of uptake predominates in C6 glioma and RBL-2H3 cells. AM404 and VDM11 were both found to decrease the uptake of 2 microM AEA into cells (IC50 values 6-11 microM), but they also inhibited rat brain FAAH (IC50 values 1-6 microM). However, when using a different FAAH assay protocol, VDM11 was a much less potent FAAH inhibitor (IC50>50 microM) regardless of the cell type and animal species used. In contrast, we confirmed that UCM707, OMDM-1 and OMDM-2 were weak inhibitors of FAAH (IC50 values >50 microM) under all conditions used. However, their potency as inhibitors of AEA cellular accumulation appears to be largely dependent on the cell type and assay conditions used. In particular, the potency of UCM707 (IC50 value > or =25 microM) was considerably lower than the submicromolar potency previously reported for U937 cells. It is concluded that the cause/effect relationship between AEA uptake and hydrolysis cannot be investigated uniquely by using supposedly selective inhibitors of each process.