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| 25mg |
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Purity: ≥98%
LY2183240 is a novel, potent and highly potent inhibitor of FAAH (fatty acid amide hydrolase) and a blocker of anandamide uptake with IC50 of 270 pM. LY2183240 inhibits the reuptake of the endocannabinoid anandamide and also acts as an inhibitor of fatty acid amide hydrolase (FAAH), the primary enzyme responsible for degrading anandamide. LY-2183240 has been shown to produce both analgesic and anxiolytic effects in animal models. LY-2183240 has relatively poor selectivity and also inhibits several other enzyme side targets. Consequently, it was never developed for clinical use, though it remains widely used in research, and has also been sold as a designer drug.
| Targets |
Anandamide (AEA) transporter binding site / Anandamide uptake inhibitor (IC₅₀ = 270 ± 29.4 pM in functional uptake assay) [1]
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| ln Vitro |
LY2183240 potently inhibits functional [¹⁴C]anandamide uptake in RBL-2H3 cells with an IC₅₀ of 270 ± 29.4 pM. [1]
LY2183240 competitively displaces the binding of its radiolabeled analog [¹²⁵I]LY2318912 to P2 membranes prepared from RBL-2H3 cells, wild-type HeLa (FAAH⁻/⁻) cells, and human FAAH-transfected HeLa cells, with a Kd of 540 ± 170 pM. This high-affinity binding site is distinct from the enzyme fatty acid amide hydrolase (FAAH). [1] The binding characteristics (Kd and Bmax) of the identified site are similar in cells expressing or lacking FAAH, confirming that the binding site is independent of FAAH. [1] |
| ln Vivo |
LY2183240 (3-30 mg/kg; ip) dose-dependently reduced formalin-induced painful paw-licking behavior in a model of persistent pain mechanisms involving formalin [1].
Intraperitoneal (i.p.) administration of LY2183240 in male Sprague-Dawley rats produced a dose-dependent increase in anandamide concentration in the cerebellum (ED₅₀ = 1.37 ± 0.980 mg/kg). [1] In the formalin-induced persistent pain model, i.p. administration of LY2183240 dose-dependently attenuated paw-licking pain behavior in both the early (0-5 min) and late (11-40 min) phases. [1] A subthreshold dose of LY2183240 (3 mg/kg, i.p.) combined with anandamide significantly decreased formalin-induced late-phase pain behavior (64.6 ± 15.5% reduction from vehicle control). [1] |
| Enzyme Assay |
FAAH enzymatic activity was measured to confirm the independence of the identified binding site from FAAH. P2 plasma membrane preparations from different cell lines were incubated with 5 nM [³H]anandamide. Reactions were terminated by extraction with chloroform/methanol, and the production of [³H]ethanolamine in the aqueous phase was quantified by liquid scintillation counting. This assay confirmed robust FAAH activity in RBL-2H3 and FAAH-transfected HeLa cells, and no measurable activity in wild-type HeLa (FAAH⁻/⁻) cells. [1]
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| Cell Assay |
Anandamide Uptake Assay: RBL-2H3 cells were plated in 96-well plates. Growth medium was replaced with uptake buffer (containing HEPES, NaCl, KCl, KH₂PO₄, CaCl₂, glucose, pH 7.4). Cells were pre-incubated with test compounds (e.g., LY2183240) for 10 minutes in buffer containing 1% fatty-acid-free BSA. Uptake was initiated by adding 5 µM [¹⁴C]anandamide. After incubation (times ranging from 1 to 20 hours, optimized for assay type), total accumulated substrate was quantified by scintillation counting. Inhibition curves were fitted to a single-site model to determine IC₅₀ values. [1]
Saturation and Competition Binding Assay: Ligand binding assays were performed using P2 membrane proteins in uptake buffer with 0.3% fatty-acid-free BSA at 30°C. Membranes were incubated with [¹²⁵I]LY2318912 in the presence or absence of competing compounds (e.g., LY2183240) for 30 minutes. Reactions were terminated by harvesting membranes onto filter mats, which were washed, dried, and counted. Specific binding was defined as total binding minus binding in the presence of 10 µM LY2183240. Saturation and competition data were analyzed to determine Kd, Bmax, and Ki values. [1] |
| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat (formalin pain model) [1]
Doses: 3, 10, 30 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results: In the formalin model of persistent pain, Formalin-induced paw licking pain behavior is attenuated in a dose-dependent manner. Brain Anandamide Measurement: Male Sprague-Dawley rats (200-250 g) received intraperitoneal (i.p.) injections of LY2183240 or vehicle. Ninety minutes post-injection, cerebellar tissue was collected, and anandamide levels were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). [1] Formalin Pain Model: Male Sprague-Dawley rats (200-250 g) received a subcutaneous (s.c.) injection of 50 µl of 5% formalin into the plantar surface of the right hind paw to induce persistent pain. LY2183240 was administered intraperitoneally (i.p.) at specified doses. Paw-licking behavior was recorded in 5-minute blocks for 60 minutes post-formalin injection. Data were analyzed as total events or separated into early (0-5 min) and late (11-40 min) phases. [1] Rotorod Test (Motor Function): Male Sprague-Dawley rats (200-250 g) were trained on an accelerating rotarod 24 hours before testing. On the test day, rats received i.p. injections of LY2183240 or vehicle. Motor coordination and control were assessed by measuring the time spent on the rotarod at 30 and 90 minutes post-injection. [1] |
| ADME/Pharmacokinetics |
Following intraperitoneal injection of LY2183240, the ED₅₀ level of arachidonic acid ethanolamine (anandamide) in the cerebellum of rats increased by 1.37 ± 0.980 mg/kg. [1]
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| Toxicity/Toxicokinetics |
At a dose of 30 mg/kg (intraperitoneal injection), LY2183240 did not cause significant behavioral changes or performance deficits in the rotarod test in rats, indicating that this dose did not cause significant impairment of motor function. [1] This study suggests that blocking the arachidonic acid ethanolamine transporter with LY2183240 may have fewer side effects than direct cannabinoid receptor agonists because it does not produce the reduction in motor function typically associated with CB₁ receptor activation. [1]
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| References |
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| Additional Infomation |
N,N-Dimethyl-5-[(4-phenylphenyl)methyl]-1-tetrazolium carboxamide belongs to the biphenyl class of compounds. LY-2183240 is an endogenous cannabinoid reuptake/degradation inhibitor. LY2183240 (5-biphenyl-4-ylmethyl-tetrazolium-1-carboxylic acid dimethylamide) is a potent competitive small molecule inhibitor that inhibits the uptake of arachidonic acid ethanolamine, which has a different structure from arachidonic acid ethanolamine molecules. [1] It was used as a parent compound for the development of a radiolabeled/photoaffinity probe (LY2318912) to identify and characterize high-affinity, saturable arachidonic acid ethanolamine transporter binding sites. [1]
This mechanism proposes that LY2183240 blocks the reuptake/transport of the endocannabinoid anandamide, thereby increasing its extracellular levels and enhancing its signaling at the active release site, providing a potential strategy for modulating the endocannabinoid system with potentially fewer side effects than direct receptor agonists. [1] This drug showed efficacy in a persistent pain model (formalin trial). [1] |
| Molecular Formula |
C17H17N5O
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|---|---|
| Molecular Weight |
307.35000
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| Exact Mass |
307.143
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| CAS # |
874902-19-9
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| PubChem CID |
11507802
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| Appearance |
White to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
506.1±53.0 °C at 760 mmHg
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| Melting Point |
87-88ºC
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| Flash Point |
259.9±30.9 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.640
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| LogP |
2.15
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
23
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| Complexity |
388
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
CUCQDDZYZNBQFE-KUNNFNOCSA-N
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| InChi Code |
InChI=1S/C12H10ClN5O5S2/c13-3-1-24-10-6(9(20)18(10)7(3)11(21)22)16-8(19)5(17-23)4-2-25-12(14)15-4/h2,6,10,23H,1H2,(H2,14,15)(H,16,19)(H,21,22)/b17-5-/t6-,10-/m1/s1
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| Chemical Name |
5-([1,1'-biphenyl]-4-ylmethyl)-N,N-dimethyl-1H-tetrazole-1-carboxamide
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| Synonyms |
LY2183240; LY-2183240; LY 2183240.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~162.68 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.13 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2536 mL | 16.2681 mL | 32.5362 mL | |
| 5 mM | 0.6507 mL | 3.2536 mL | 6.5072 mL | |
| 10 mM | 0.3254 mL | 1.6268 mL | 3.2536 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Mean (±SEM) % FPS in male and female HAP mice in each LY2183240 dose group during the first (test 1) and second (test 2) FPS test.
Mean (±SEM) % FPS in male and female LAP mice for each LY2183240 dose group during the first (test 1) and second (test 2) FPS test.Psychopharmacology (Berl). 2010 Dec;212(4):571-83. |
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 Mean (±SEM) alcohol (g/kg;a) and total fluid (ml/kg;b) intake in HAP mice within each LY2183240 dose group during the 2-h limited access session on the first (drug day 1) and second (drug day 2) drug testing days.Psychopharmacology (Berl). 2010 Dec;212(4):571-83. |
 Mean (±SEM) second per minute (s/min) on alcohol-paired floor (post-test–pre-test difference score) in male and female HAP mice in each LY2183240 dose group during the first and last 30 min of each of the three preference tests.Psychopharmacology (Berl). 2010 Dec;212(4):571-83. |
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