Encenicline hydrochloride

SKU: orb1305795

Description

Encenicline hydrochloride (EVP-6124 hydrochloride) is a selective partial agonist of the α7 nicotinic acetylcholine receptor. It is utilized in research to investigate cognitive function and has been studied in preclinical models for neurological disorders.

Research Area

Neuroscience

Key Properties

• CAS Number: 550999-74-1
• MW: 357.3
• Purity: 99.85% (May vary between batches)
• Formula: C₁₆H₁₇ClN₂OS·HCl
• SMILES: Cl.Clc1cccc2cc(sc12)C(=O)NC1CN2CCC1CC2
• Target: AChR
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (2.8 mM);DMSO:10 mg/mL (27.99 mM)

Bioactivity

• In Vivo:
  EVP-6124 hydrochloride demonstrates effective brain penetration and sufficient exposure duration, showing significant memory restoration at a dose of 0.3 mg/kg orally in scopolamine-induced memory impairment in rats, measured by an object recognition task (ORT). When combined with donepezil at sub-efficacious doses (0.1 mg/kg, orally for donepezil and 0.03 mg/kg, orally for EVP-6124), full memory restoration is achieved, suggesting synergistic effects. In a 24-hour retention natural forgetting test, EVP-6124 at 0.3 mg/kg orally enhances memory, an effect inhibited by the selective α7 nAChR antagonist methyllycaconitine, validating the involvement of α7 nAChR in the mechanism of action. EVP-6124 binds to rat plasma proteins at a moderate level with a fractional unbound average of 11% and shows dose-proportional pharmacokinetics over a 0.1-30 mg/kg oral dose range. Peak times (Tmax) are recorded at 4 hours in plasma and 2 hours in the brain, with brain concentrations maintaining from 2 to 8 hours, and brain-to-plasma (B:P) ratios ranging from 1.7 to 5.1. Additionally, at a dose of 0.4 mg/kg intraperitoneally, EVP-6124 achieves peak brain concentration in 2 hours, maintaining effective levels for at least 4 hours, and notably increases NMDAR saturation index in wild-type mice without affecting wakefulness or locomotion.
• In Vitro:
  EVP-6124 hydrochloride displaces [3H]-MLA (Methyllycaconitine) (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). EVP-6124 is approximately 300 fold more potent than the natural agonist ACh (Ki=3 μM), measured in binding assays using [3H]-MLA. EVP-6124 inhibits the 5-HT3 receptor by 51% at 10 nM, the lowest concentration tested. Evaluation of the human 5-HT2B receptor expressed in CHO cells demonstrates displacement of [3H]-mesulergine (Ki=14 nM) and only antagonist activity in the rat gastric fundus assay at an IC50 of 16 μM. In binding and functional experiments, EVP-6124 shows selectivity for α7 nAChRs and does not activate or inhibit heteromeric α4β2 nAChRs.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Nicotinic acetylcholine receptors, nAChR, inhibit, Encenicline, Encenicline Hydrochloride, Encenicline hydrochloride, EVP 6124, EVP 6124 Hydrochloride, EVP6124, EVP-6124, EVP-6124 (hydrochloride), EVP-6124 hydrochloride, EVP-6124 Hydrochloride, EVP6124 Hydrochloride, Inhibitor, α7 nAChR

Compound Identifiers

PubChem CID

66787254