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Encenicline (EVP-6124; MT-4666) is a novel partial agonist of α7 nicotinic acetylcholine receptor. EVP-6124 enhances dopamine, acetylcholine, and glutamate efflux in rat cortex and nucleus accumbens. EVP-6124 improves memory performance by potentiating the acetylcholine response of α7 nicotinic acetylcholine receptors.
| ln Vitro |
Encenicline (EVP-6124) has been substituted for [3H]-MLA (methylaconitine) (Ki=9.98 nM, pIC50=7.65±0.06, n=3) and [125I]-α-bungarotoxin (Ki=4.33 nM, pIC50=8.07±0.04), n=3). By using a [3H]-MLA binding test, encenicline (EVP-6124) was found to be around 300 times more powerful than the natural agonist ACh (Ki=3 μM). At 10 nM, the lowest concentration tested, encenicline hydrochloride inhibits 5-HT3 receptors by 51%. An assessment of human 5-HT2B receptors produced in CHO cells revealed only antagonist action in the rat fundus assay, with an IC50 of 16 μM, and displacement of [3H]-mesoergot (Ki=14 nM). Encenicline (EVP-6124) did not inhibit or activate heteromeric α4β2 nAChR in binding or functional tests, however it did demonstrate selectivity for α7 nAChR[1].
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| ln Vivo |
Ensenilin hydrochloride has an adequate exposure period and strong brain penetration. When rats treated with scopolamine (0.1 mg/kg, ip) were given encenicline hydrochloride (0.3 mg/kg, po), their memory function was greatly restored during the object recognition test (ORT). On this test, memory was not improved by donepezil (0.1 mg/kg) or ensenicline hydrochloride (0.03 mg/kg), however memory was entirely recovered when these sub-effective dosages were coadministered. The spontaneous forgetting test (ORT) demonstrated a 24-hour retention period. The administration of Encenicline hydrochloride (0.3 mg/kg) po resulted in an improvement in memory. Methylaconitine (0.3 mg/kg, ip or 10 μg, icv), a specific α7 nAChR antagonist, prevented this improvement. ..Rat plasma proteins exhibited a moderate binding of encenicline hydrochloride, with a mean fu of 0.11±0.01 (mean±SD), or 11%. Throughout the oral dosage range of 0.1–30 mg/kg, escenicline hydrochloride shows proportionate dose escalation. Tmax was 4 hours for plasma and 2 hours for the brain; however, the concentrations in the brain did not change between 2 and 8 hours. The B:P ratio is 1.7–5.1 during the first eight hours[1]. Encenicline hydrochloride (0.4 mg/kg, intraperitoneal injection) reaches peak brain concentrations two hours after delivery and maintains effective concentrations for at least four hours, according to pharmacokinetic studies. Without producing extended wakefulness or increased locomotor activity, encenicline hydrochloride administered to WT mice at ZT0 (0.4 mg/kg ip single dose) significantly elevated the saturation index of NMDAR in slices retrieved 4 hours later [ 2].
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| References |
[1]. Prickaerts J, et al. EVP-6124, a novel and selective α7 nicotinic acetylcholine receptor partial agonist, improves memory performance by potentiating the acetylcholine response of α7 nicotinic acetylcholine receptors. Neuropharmacology. 2012 Feb;62(2):109
[2]. Thomas Papouin, et al. Septal Cholinergic Neuromodulation Tunes the Astrocyte-Dependent Gating of Hippocampal NMDA Receptors to Wakefulness. Neuron. 2017 May 17;94:1-15. [3]. Papouin T, et al. Septal Cholinergic Neuromodulation Tunes the Astrocyte-Dependent Gating of Hippocampal NMDA Receptors to Wakefulness. Neuron. 2017 May 17;94(4):840-854.e7. [4]. Maehara S, et al. Pharmacological characterization of a novel potent, selective, and orally active phosphodiesterase 2A inhibitor, PDM-631. Eur J Pharmacol. 2017 Sep 15;811:110-116 |
| Molecular Formula |
C16H18CL2N2OS
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| Molecular Weight |
357.2979
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| CAS # |
550999-74-1
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| Related CAS # |
Encenicline;550999-75-2
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| SMILES |
O=C(C1=CC2=CC=CC(Cl)=C2S1)N[C@H]3CN4CCC3CC4.[H]Cl
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| InChi Key |
OIJYTJGIDVTCFF-ZOWNYOTGSA-N
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| InChi Code |
InChI=1S/C16H17ClN2OS.ClH/c17-12-3-1-2-11-8-14(21-15(11)12)16(20)18-13-9-19-6-4-10(13)5-7-19/h1-3,8,10,13H,4-7,9H2,(H,18,20)1H/t13-/m0./s1
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| Chemical Name |
(R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride.
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| Synonyms |
EVP-6124 HCl EVP 6124 EVP6124 MT-4666 MT4666 MT 4666 Encenicline HCl.
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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 (~139.94 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.00 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.00 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7988 mL | 13.9938 mL | 27.9877 mL | |
| 5 mM | 0.5598 mL | 2.7988 mL | 5.5975 mL | |
| 10 mM | 0.2799 mL | 1.3994 mL | 2.7988 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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