α4β2 nachr

Rivanicline 2HCl is a selective neuronal nicotinic receptor inhibitor with a high affinity for the α4β2 subtype.

Biricodar dicitrate (VX-710) is a potent MDR inhibitor with no anticancer activity and can be used to study prostate cancer.

Thiacloprid is a neonicotinoid insecticide that acts as a selective agonist at insect nicotinic acetylcholine receptors (nAChRs) with IC50values of 2.7 and 860 nM forDrosophilanAChRs and M10 mouse fibroblast cells expressing α4β2 subunit-containing nAChRs, respectively.1It is active against aphids, whiteflies, various species of beetle, andLepidopteraspecies when used at concentrations ranging from 48 to 180 g AI hectare.2It has anti-estrogenic activity in a yeast estrogen screen and is toxic to adult female houseflies and mice (LD50s = 0.03 and 28 mg kg, respectively).1,3Formulations containing thiacloprid have been used in the control of insects in agriculture. 1.Tomizawa, M., and Casida, J.E.Selective toxicity of neonicotinoids attributable to specificity of insect and mammalian nicotinic receptorsAnnu. Rev. Entomol.48339-364(2003) 2.Elbert, A., Erdelen, C., Kuhnhold, J., et al.Thiacloprid, a novel neonicotinoid insecticide for foliar applicationProc. Brighton Crop. Prot. Conf. - Pests and Diseases121-26(2000) 3.Westlund, P., and Yargeau, V.Investigation of the presence and endocrine activities of pesticides found in wastewater effluent using yeast-based bioassaysSci. Total Environ.607-608744-751(2017)

Urethane (Ethylurethane) was an antineoplastic agent .Now is used for other medicinal purposes.

Desformylflustrabromine hydrochloride (dFBr hydrochloride) is a selective agonist of nicotinic acetylcholine receptor (nAChR) in α4β2 neurons, with pEC50 of 6.48.

TC-2216 is a partial agonist at the neural nicotinic acetylcholine receptor and is used to treat anxiety and depression.

UB 165 fumarate is an agonist of the nAChR, a partial agonist of the α4β2 subtype, and a full agonist of the α3β2 subtype, with a Ki value of 0.27 nM for binding to [3H]-nicotine measured in rat brain.

Ispronicline (TC-1734) An orally active, selective, and potent α4β2 nAChR partial agonist with antidepressant, neuroprotective, and long-lasting cognitive effects.Ispronicline has a high affinity for the α4β2 nAChR with a Ki= 11 nM.

Benzethonium chloride (Quatrachlor) is a synthetic quaternary ammonium salt with surfactant, antiseptic, and broad spectrum antimicrobial properties.

Adiphenine hydrochloride (Patrovina), a nicotinic receptor inhibitor, can be used as an antispasmodic drug.

Pozanicline hydrochloride is an orally bioavailable nicotinic acetylcholine receptor (nAChR) agonist with a Ki of 16.7 nM for binding to [3H]cytisine sites[1]. Pozanicline hydrochloride is an α4β2-selective nAChR agonist, which binds to rat brain α4β2 nAChR with a Ki of 17 nM while binding to α7 nAChR is insignificant[2].

DMAB-anabaseine dihydrochloride (N,N-dimethyl-4-[(E)-(6-pyridin-3-yl-3,4-dihydro-2H-pyridin-5-ylidene)methyl]aniline;dihydrochloride) is an α7-containing neuronal nicotinic receptor partial agonist and an antagonist at α4β2 and other nicotinic receptors.

nAChR agonist that displays selectivity for α4β2

Rivanicline hemioxalate, also known as RJR-2403 hemioxalate or (E)-Metanicotine hemioxalate, is a chemical compound acting as a neuronal nicotinic receptor agonist with pronounced selectivity for the α4β2 receptor subtype, showing over 1,000-fold greater selectivity for this subtype (Ki=26 nM) compared to α7 receptors (Ki=3.6 μM). Its in vitro studies demonstrate no significant activation of nAChRs in PC12 cells, muscle type nAChRs, or muscarinic receptors at concentrations up to 1 mM. Furthermore, Rivanicline displayed less than one-tenth the potency of nicotine in inducing ileum contraction, with substantially lower efficacy, and failed to antagonize nicotine-induced stimulation of muscle or ganglionic nAChR functions, with an IC50 value greater than 1 mM. Chronic exposure to Rivanicline at 10 microM led to up-regulation of high-affinity nAChRs in M10 cells, mimicking effects observed with nicotine. In vivo studies revealed that Rivanicline significantly reversed scopolamine-induced amnesia and improved working and reference memory in a rat model, while being 15 to 30 times less potent than nicotine in affecting body temperature, respiration, and other physiological responses. Metanicitone's potency was approximately five times lower than nicotine in tail-flick tests following subcutaneous administration, yet slightly more potent upon central administration.

AN317 is a selective agonist for the nicotinic acetylcholine receptor (nAChR) containing α6β2, with dissociation constants (Ki) of 6.2 nM and 4.1 nM for the α6 α3β2β3 and α4β2 receptor subtypes, respectively. It induces dopamine release in rat striatal synaptosomes, enhances the activity of dopaminergic neurons in the substantia nigra, and exhibits protective effects against the dopaminergic neurotoxin MPP+ in rat neurons. AN317 also demonstrates favorable pharmacokinetic properties in rats and permeability across the blood-brain barrier (BB).

NS3861 fumarate is an agonist of nicotinic acetylcholine receptors (nAChRs), acting as a partial agonist at α3β4 nAChR and binding with high affinity to heteromeric α3β4 nAChR, with binding Ki values of 0.62, 25, 7.8, 55 nM for α3β4, α3β2, α4β4, α4β2, respectively[1].

DPNB-ABT 594 is a nitrobenzyl-caged ABT 594, a selective α4β2 nAChR agonist. One-photon uncaging evokes large inward currents and Ca2+transients on cell bodies and dendrites of medial habenular neurons in mouse brain slices. Two-photon uncaging induces fast nAChR-mediated currents. Photolyzed with high quantum yield of 0.20. Effective photolysis occurs using one- or two-photon excitation; one-photon uncaging requires illumination at 410 nm for 1.5-3 ms; two-photon uncaging requires illumination with appropriate two photon pulse laser at 710 nm for ~2 ms.

NS-3956 fumaric acid salt is a partial nAChR α4β2 LS and HS agonist with analgesic properties.

suvn-911 is a potent and selective antagonist of neuronal nicotinic acetylcholine α4β2 receptor (Ki = 1.5 nM) with antidepressant activity.

Myosmine is a minor tobacco alkaloid that is structurally related to nicotine.

Compound 8, identified as a selective alpha4beta2 (α4β2) neuronal acetylcholine receptor (nAChR) agonist, demonstrates a dissociation constant (Kd) of 26 nM, indicating high affinity for this receptor subtype.

Iptakalim, a lipophilic para-amino compound, is a novel ATP-sensitive potassium channel (KATP) opener, as well as an α4β2-containing nicotinic acetylcholine receptor (nAChR) antagonist. Iptakalim is also a K(ir) 6.1 SUR2B activator that can attenuate hypoxia-induced pulmonary arterial hypertension in rats by endothelial function protection.

Pozanicline dihydrochloride (ABT-089 dihydrochloride) is an orally bioavailable agonist of the nicotinic acetylcholine receptor (nAChR) with a Ki of 16.7 nM.

High affinity and subtype selective α6β2 and α4β2 partial agonist (Ki values are 12 and 26nM for rat α6β2 and α4β2 receptors respectively). Has low affinity for α3β4 and α7 receptors (Ki values are 4.8 and 13 μM for human α3β4 and rat α7 receptors respectively). Stimulates dopamine release from striatal slices in vitro. Attenuates nicotine-induced self-administration and conditional place preference in rats. Sala et al (2013) CC4, a dimer of cytisine, is a selective partial agonist at α4β2/α6β2 nAChR with improved selectivity for tobacco smoking c Br.J.Pharmacol. 168 835 PMID:22957729 |Riganti et al (2005) Long-term exposure to the new nicotinic antagonist 1,2-bisN-cytisinylethane upregulates nicotinic receptor subtypes of SH-SY5Y human neuroblastoma cells. Br.J.Pharmacol. 146 1096 PMID:16273122 |Carbonnelle et al (2003) Nitrogen substitution modifies the activity of cytisine on neuronal nicotinic receptor subtypes. Eur.J.Pharmacol. 471 85 PMID:12818695