α3β4 nachr

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

PNU-282987 is a selective α7 nicotinic acetylcholine receptor(α7 nAChR) agonist with Ki of 26 nM; no affinity for α1β1γδ and α3β4 nAChRs (IC50 ≥ 60 μM).

Dexmecamylamine ((+)-Mecamylamine) acts as an antagonist of nicotinic acetylcholine receptors (nAChR), effectively inhibiting α3β4, α4β2, α7, and α1β1γδ receptors, with an IC50 in the micromolar range. It also exhibits anxiolytic and antidepressant-like effects.

α3β4 nAChR antagonist

α-Conotoxin ImI is a conotoxin that has been found inC. imperialisand has receptor antagonist and anticancer activities.1It is a peptide antagonist of homomeric α7 nicotinic acetylcholine receptors (nAChRs; IC50= 220 nM). α-Conotoxin ImI is selective for α7 nAChRs over α2β2, α3β2, α4β2, α2β4, α3β4, α4β4, and α1β1γδ subunit-containing nAChRs at 5 μM but does inhibit homomeric α9 nAChRs (IC50= 1,800 nM). Administration of paclitaxel in micelles containing α-conotoxin ImI decreases tumor growth in an MCF-7 mouse xenograft model.2Intracerebroventricular, but not intraperitoneal, administration of α-conotoxin ImI (20 nmol/animal) induces seizures in rats.3 1.Johnson, D.S., Martinez, J., Elgoyhen, A.B., et al.α-Conotoxin ImI exhibits subtype-specific nicotinic acetylcholine receptor blockade: Preferential inhibition of homomeric α7 and α9 receptorsMol. Pharmacol.48(2)194-199(1995) 2.Mei, D., Lin, Z., Fu, J., et al.The use of α-conotoxin ImI to actualize the targeted delivery of paclitaxel micelles to α7 nAChR-overexpressing breast cancerBiomaterials4252-65(2015) 3.McIntosh, J.M., Yoshikami, D., Mahe, E., et al.A nicotinic acetylcholine receptor ligand of unique specificity, α-conotoxin ImIJ. Biol. Chem.269(24)16733-16739(1994)

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

Aspergillimide is a fungal metabolite originally isolated from A. japonicus.1 It reduces nicotinic acetylcholine receptor (nAChR) peak and slowly-desensitizing amplitudes induced by acetylcholine in silkworm (B. mori) larval neurons (IC50s = 20.2 and 39.6 nM, respectively) but has no effect on chicken α3β4-, α4β2-, and α7-containing nAChRs.2 Dietary administration of aspergillimide A (10 μg/g of diet) induces paralysis in silkworm fourth instar larvae.1 Aspergillimide A (10 and 20 mg/kg) reduces T. colubriformis fecal egg count in gerbils.3References1. Hayashi, H., Nishimoto, Y., Akiyama, K., et al. New paralytic alkaloids, asperparalines A, B and C, from Aspergillus japonicus JV-23. Biosci. Biotechnol. Biochem. 64(1), 111-115 (2000).2. Hirata, K., Kataoka, S., Furutani, S., et al. A fungal metabolite asperparaline a strongly and selectively blocks insect nicotinic acetylcholine receptors: The first report on the mode of action. PLoS One 6(4), e18354 (2011).3. Banks, R.M., Blanchflower, S.E., Everett, J.R., et al. Novel anthelmintic metabolites from an Aspergillus species; the aspergillimides. J. Antibiot. (Tokyo) 50(10), 840-846 (1997). Aspergillimide is a fungal metabolite originally isolated from A. japonicus.1 It reduces nicotinic acetylcholine receptor (nAChR) peak and slowly-desensitizing amplitudes induced by acetylcholine in silkworm (B. mori) larval neurons (IC50s = 20.2 and 39.6 nM, respectively) but has no effect on chicken α3β4-, α4β2-, and α7-containing nAChRs.2 Dietary administration of aspergillimide A (10 μg/g of diet) induces paralysis in silkworm fourth instar larvae.1 Aspergillimide A (10 and 20 mg/kg) reduces T. colubriformis fecal egg count in gerbils.3 References1. Hayashi, H., Nishimoto, Y., Akiyama, K., et al. New paralytic alkaloids, asperparalines A, B and C, from Aspergillus japonicus JV-23. Biosci. Biotechnol. Biochem. 64(1), 111-115 (2000).2. Hirata, K., Kataoka, S., Furutani, S., et al. A fungal metabolite asperparaline a strongly and selectively blocks insect nicotinic acetylcholine receptors: The first report on the mode of action. PLoS One 6(4), e18354 (2011).3. Banks, R.M., Blanchflower, S.E., Everett, J.R., et al. Novel anthelmintic metabolites from an Aspergillus species; the aspergillimides. J. Antibiot. (Tokyo) 50(10), 840-846 (1997).

(Rac)-CP-601927 hydrochloride is the racemate form of CP-601927, a nicotinic acetylcholine receptor (nAChR) agonist, with Ki values of 1.2 nM for α4β2 and 102 nM for α3β4 nAChR.

TC-2559 idifumarate is a CNS-selective, orally active α4β2 subtype of nicotinic acetylcholine receptor (nAChR) partial agonist with an EC50 of 0.18 μM. It exhibits selectivity for α4β2 receptors over α2β4, α4β4, and α3β4 receptors, with EC50s ranging from 10 to 30 μM. TC-2559 difumarate also demonstrates antinociceptive effects.

Varenicline (CP 526555) is a selective partial agonist of the α4β2 nAChR and a full agonist of the α3β4 nAChR and α7 nAChR to help smokers with cardiovascular disease and COPD quit smoking.

AT-1001 is an α3β4 nAChR partial agonist. AT-1001 attenuates stress-induced reinstatement of nicotine seeking in a rat model of relapse and induces minimal withdrawal in dependent rats. AT-1001 also potently and reversibly blocks epibatidine-induced inward currents in HEK cells transfected with α3β4 nAChR. Importantly, AT-1001 potently and dose-dependently blocks nicotine self-administration in rats, without affecting food responding. When tested in a nucleus accumbens (NAcs) synaptosomal preparation, AT-1001 inhibits nicotine-induced [³H]dopamine release poorly and at significantly higher concentrations compared with mecamylamine and conotoxin MII.

α-Conotoxin Vc1.1 TFA is a peptide isolated from Conus victoriae and a selective nAChR antagonist that inhibits α3α5β2, α3β2 and α3β4, reversing mechanical allodynia in neuropathic pain models and can be used to study neuropathic chronic pain. α-Conotoxin Vc1.1 TFA inhibits human dorsal root ganglion nerve excitability and mouse colon nociception via GABA(B) receptors.

α-Conotoxin AuIB TFA, a potent selective antagonist of the α3β4 nicotinic acetylcholine receptor (nAChR), effectively inhibits nAChRs expressed in Xenopus oocytes, demonstrating an inhibitory concentration (IC50) of 0.75 μM [1].

α-Conotoxin BuIA is a paralytic peptide neurotoxin that acts as a competitive antagonist of nicotinic acetylcholine receptors (nAChR), with inhibitory concentration 50 (IC50) values of 0.258 nM for α6 α3β2, 1.54 nM for α6 α3β4, and 5.72 nM for α3β2. It serves to differentiate between nAChRs containing the β2- and β4-subunits and selectively inhibits αxβ2 nAChRs, exhibiting a potency hierarchy of α6>α3>α2>α4 [1].

α-Conotoxin TxID is a potent antagonist of the α3β4 nicotinic acetylcholine receptor (nAChR) with an inhibitory half-maximal inhibitory concentration (IC50) of 12.5 nM. Its inhibitory activity is weaker against the closely related α6 α3β4 nAChR, with an IC50 of 94 nM. This compound holds potential for the development of novel smoking cessation drugs [1].

α-Conotoxin AuIA, isolated from Conus aulicus [1], is a potent and selective inhibitor of α3β4 nicotinic acetylcholine receptors (nAChRs).

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].

NS3861 is an agonist of nicotinic acetylcholine receptors (nAChRs) that binds with high affinity to heteromeric α3β4 and α4β2 nAChRs, displaying β-subunit preference and no activation at α4-containing receptors. The maximal efficacy of NS3861 depends on the ligand-binding domain, and a serine to threonine substitution in the principal subunit may explain the lack of activation at α4-containing receptors.

Aristoquinoline (Compound 1), an alkaloid isolated from Aristotelia chilensis, exhibits α3β4 nAChR inhibitory activity [1].

α-Conotoxin MII is a highly potent and selective competitive antagonist for α3β2 subunit-containing nicotinic receptors (IC50 = 0.5 - 3.5 nM at α3β2 expressed in Xenopus oocytes). Also potently blocks β3-containing neuronal nicotinic receptors. Displays >