| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
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| Targets |
5-HT2A Receptor (IC50 = 5.8 nM); 5-HT2C Receptor (IC50 = 120 nM)
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|---|---|
| ln Vitro |
Other 5-HT kinases are weakly inhibited by eplivanserin hemifumarate (SR 46349B), with IC50 values of 0.12 μM for pig cortical 5-HT1C, 14 μM for rat hippocampus 5-HT1A, and 16 μM for rat stnatum 5-HT1B, Ox) caudate nucleus 5-HT1D. With IC50 values of 3.4 μM, 1.0 μM, 5.0 μM, and 39 μM, respectively, eplivanserin also inhibits rat cortical epinephrine α1 and α2, rat whole brain histamine H1, Na+ channels, and rat striatum dopamine D1 and D2. , 9 μM, and 28 μM, in that order [1].
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| ln Vivo |
Eplivanserin halffumarate (SR 46349B) has an ED50 of 0.087 mg/kg following intraperitoneal injection and 0.097 mg/kg following oral administration in mice [1]. It inhibits the 5-HT2 receptor binding of [3H]ketanserin. After multiple cocaine treatments, SR 46349B (0.25–1 mg/kg; i.p.) prevents rats from becoming hyperactive due to cocaine [2].
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| Enzyme Assay |
A new potent, selective and p.o. active serotonergic [5-hydroxytryptamine (5-HT2)] receptor antagonist, Eplivanserin (SR-46349) [trans, 4-([3Z)3-(2-dimethylaminoethyl)oxyimino-3(2-flurophenyl++ +)propen-1-yl]phenol hemifumarate) has been characterized by a series of "in vitro" and "in vivo" methods. Based upon binding studies with 5-HT2 receptors in rat brain cortical membranes and blockade of 5-HT-induced contractions in isolated tissues (rabbit thoracic aorta, rat jugular vein, rat caudal artery, rat uterus and guinea pig trachea), Eplivanserin (SR-46349) showed high affinity for 5-HT2 receptors. Furthermore, Eplivanserin (SR-46349) displayed moderate affinity for the 5-HT1C receptor and had no affinity for the other 5-HT1 subclass (5-HT1A, 5-HT1B or 5-HT1D), dopamine (D1 or D2), "alpha" adrenergic (alpha-1 or alpha-2), sodium and calcium channel and histamine (H1) receptors. It did not interact with histamine (H1), alpha-1 adrenergic and 5-HT3 receptors in smooth muscle preparations. No inhibition of the uptake of norepinephrine, dopamine or 5-HT was seen. Based upon blockade of pressor responses to 5-HT in pithed rats and in vivo binding studies in mice, SR 46349B was found to be a potent and p.o. active 5-HT2 receptor antagonist with a relatively long duration of action. Behavioral experiments, including mescaline- and 5-hydroxytryptophan-induced head twitches and learned helplessness, as well as sleep-waking cycle and EEG spectral parameter studies, indicated that SR 46349B has a classical 5-HT2 psychopharmacological antagonist profile.[1]
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| Animal Protocol |
The 5-HT2AR antagonist Eplivanserin (SR-46349) also blocked cocaine-evoked hyperactivity following repeated cocaine treatment, whereas the other 5-HT2R ligands were ineffective. When any of the 5-HT2R ligands was coadministered with cocaine during the treatment regimen (10 mg/kg/day for 5 days), the development of sensitization was unchanged as measured by the level of cocaine-evoked hyperactivity upon challenge 5 days after termination of the treatment. The present study implies that 5-HT2AR and 5-HT2CR exert oppositional influence upon hyperactivity evoked by acute administration of cocaine; this balance is altered following repeated cocaine administration.
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| References |
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| Additional Infomation |
Drug Indication
Insomnia The role of serotonin (5-hydroxytryptamine; 5-HT) 5-HT2 receptor subtypes (5-HT2AR, 5-HT2BR, and 5-HT2CR) in acute cocaine-evoked hyperactivity was compared with their contribution to the development and expression of locomotor sensitization upon repeated, intermittent treatment with cocaine (10 mg/kg/day for 5 days) in male Wistar rats. Cocaine-evoked hyperactivity was significantly enhanced by pretreatment with the preferential 5-HT2AR agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and the 5-HT2CR antagonist SDZ SER-082 [(+)-cis-4,5,7a,8,9,10,11,11a-octahydro-7H-10-methylindolo(1,7-BC)(2,6) naphthyridine fumarate]. The 5-HT2AR antagonist SR 46349B [1(Z)-[2-(dimethylamino)ethoxyimino]-1(2-fluorophenyl)-3-(4-hydroxyphenyl)-2(E)-propene] and the preferential 5-HT2CR agonist MK 212 [6-chloro-2-(1-piperazinyl)pyrazine HCl] (2 mg/kg) significantly attenuated acute cocaine-evoked hyperactivity; however, a lower dose of MK 212 (0.3 mg/kg) enhanced cocaine-evoked hyperactivity. The 5-HT2BR agonist BW 723C86 (1-[5-(2-thienylmethoxy)-1H-3-indolyl]propan-2-amine HCl) and the 5-HT2BR antagonist SB 204741 [N-(1-methyl-5-indolyl)-N'-(3-methyl-5-isothiazolyl) urea] had no effect on cocaine-evoked hyperactivity. Repeated treatment with cocaine alone resulted in a 2-fold increase in hyperactivity upon challenge with cocaine 5 days after termination of the cocaine regimen (sensitization). The 5-HT2AR antagonist SR 46349B also blocked cocaine-evoked hyperactivity following repeated cocaine treatment, whereas the other 5-HT2R ligands were ineffective. When any of the 5-HT2R ligands was coadministered with cocaine during the treatment regimen (10 mg/kg/day for 5 days), the development of sensitization was unchanged as measured by the level of cocaine-evoked hyperactivity upon challenge 5 days after termination of the treatment. The present study implies that 5-HT2AR and 5-HT2CR exert oppositional influence upon hyperactivity evoked by acute administration of cocaine; this balance is altered following repeated cocaine administration. [2] |
| Molecular Formula |
C23H25FN2O6
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|---|---|
| Molecular Weight |
444.4594
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| Exact Mass |
444.17
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| Elemental Analysis |
C, 62.15; H, 5.67; F, 4.27; N, 6.30; O, 21.60
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| CAS # |
130580-02-8
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| Related CAS # |
Eplivanserin (mixture);130581-13-4;Eplivanserin;130579-75-8
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| PubChem CID |
135456189
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| Appearance |
Typically exists as solid at room temperature
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| Boiling Point |
456.3ºC at 760mmHg
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| Flash Point |
229.8ºC
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| Vapour Pressure |
1.63E-08mmHg at 25°C
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| LogP |
3.238
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| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
56
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| Complexity |
537
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC(/C=C/C(=O)O)=O.CN(CCON/C(/C1=CC=CC=C1F)=C/C=C1/C=CC(=O)C=C/1)C.CN(CCON/C(/C1=CC=CC=C1F)=C/C=C1/C=CC(=O)C=C/1)C
|
| InChi Key |
RNLKLYQQDLHHBH-ABDBJYMXSA-N
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| InChi Code |
InChI=1S/2C19H21FN2O2.C4H4O4/c2*1-22(2)13-14-24-21-19(17-5-3-4-6-18(17)20)12-9-15-7-10-16(23)11-8-15;5-3(6)1-2-4(7)8/h2*3-12,23H,13-14H2,1-2H3;1-2H,(H,5,6)(H,7,8)/b2*12-9+,21-19-;2-1+
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| Chemical Name |
(E)-but-2-enedioic acid;4-[(E,3Z)-3-[2-(dimethylamino)ethoxyimino]-3-(2-fluorophenyl)prop-1-enyl]phenol
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| Synonyms |
Eplivanserin fumarate; Eplivanserin fumarate; Eplivanserin hemifumarate; SR-46349B; 130580-02-8; BT8UYC46KA; Eplivanserin fumarate [USAN]; SR46349B; SR 46349B; SR-46349 fumarate
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~25 mg/mL (~64.69 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2499 mL | 11.2496 mL | 22.4992 mL | |
| 5 mM | 0.4500 mL | 2.2499 mL | 4.4998 mL | |
| 10 mM | 0.2250 mL | 1.1250 mL | 2.2499 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.
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