α-Conotoxin TxID is a potent α3β4 nAChR antagonist with an IC50 value of 12.5 nM. α-Conotoxin TxID has weak inhibition activity of closely related α6/α3β4 nAChR (IC50= 94 nM). α-Conotoxin TxID has the potential for novel smoking cessation drug development[1].
α-Bungarotoxin is a competitive antagonist at nicotinic acetylcholine receptors (nAChRs). α-Bungarotoxin, a selective α7 receptor blocker, blocks α7 currents with an IC50 of 1.6 nM and has no effects on α3β4 currents at concentrations up to 3 μM[1][2].
Mecamylamine-d3 hydrochloride is the deuterium labeled Mecamylamine hydrochloride. Mecamylamine hydrochloride is an orally active, nonselective, noncompetitive nAChR antagonist that can treat various neuropsychiatric disorders. Mecamylamine hydrochloride is originally used as a ganglionic blocker in treating hypertension. Mecamylamine hydrochloride can easily crosses the blood-brain barrier[1][2].
Desformylflustrabromine hydrochloride is a selective agonist of α4β2 neuronal nicotinic acetylcholine receptor (nAChR) with a pEC50 of 6.48.
Catestatin is a 21-amino acid residue, cationic and hydrophobic peptide. Catestatin is an endogenous peptide that regulates cardiac function and blood pressure[1]. Catestatin is a non-competitive nicotinic antagonist acting through nicotinic acetylcholine receptors (nAChRs) to inhibit catecholamine release[2].
ACV1 (Vc1.1), an α-Conotoxin, is a selective α9α10 nAChR antagonist with an IC50 of 19 nM. ACV1 is ~100-fold less potent on human α9α10 vs. rat nAChRs[1].
Varenicline (CP 526555) dihydrochloride is a potent partial agonist for α4β2 nicotinic acetylcholine receptor (nAChR) with an EC50 value of 2.3 μM. Varenicline dihydrochloride is a full agonist for α3β4 and α7 nAChRs with EC50 values of 55 μM and 18 μM, respectively[2]. Varenicline dihydrochloride is a nicotinic ligand based on the structure of cytosine, and has the potential for smoking cessation treatment[5].
nAChR modulator-1, a insecticide, is a insect nAChR orthosteric modulator[1].
nAChR agonist 1 is a potent, brain-permeable, and orally efficacious positive allosteric modulator of α7 nicotinic acetylcholine receptor (α7 nAChR). nAChR agonist 1 has the EC50 of 0.32 µM in a Ca2+ mobilization assay (PNU-282987-induced, FLIPR based) in human IMR-32 neuroblastoma cells that endogenously express α7 nAChR. nAChR agonist 1 can be develpoped for the treatment of Alzheimer’s disease[1].
CVN417 is an orally active α6 subunit-containing nAChR antagonist, modulating phasic dopaminergic neurotransmission in an impulse-dependent manner. CVN417 inhibits Ca(2+) effluents mediated by nAChR subunits with IC50s of 0.086 μM (α6), 2.56 μM (α3) and 0.657 μM (α4), respectively. CVN417 attenuates resting tremor in Rodent models, displays the potential to improve movement dysfunction, in conditions such as Parkinson's disease[1].
α7 nAchR-JAK2-STAT3 agonist 1 is a potent α7 nAchR-JAK2-STAT3 agonist, with an IC50 value of 0.32 μM for nitric oxide (NO). α7 nAchR-JAK2-STAT3 agonist 1 effectively suppresses the expression of iNOS, IL-1β, and IL-6 in murine RAW264.7 macrophages. α7 nAchR-JAK2-STAT3 agonist 1 can inhibit LPS-induced NO release, NF-κB activation and cytokine production. α7 nAchR-JAK2-STAT3 can be used for researching sepsis[1].
TC-2559 idifumarate is a CNS-selective, orally active α4β2 subtype of nicotinic acetylcholine receptor (nAChR) partial agonist (EC50=0.18 μM). TC-2559 difumarate shows selectivity for α4β2 over α2β4, α4β4 and α3β4 receptors, with EC50s in the range of 10-30 µM. Antinociceptive effect[1][2].
(±)-Epibatidine is a nicotinic agonist. (±)-Epibatidine is a neuronal nAChR agonist.
GTS-21 dihydrochloride is a selective α7 nicotinic acetylcholine receptor agonist, has recently been established as a promising treatment for inflammation. Target: nAChRin vitro: GTS-21 is one of the most potent α7nAChR agonists, has been reported to attenuate pro-inflammatory cytokine production, improve outcomes in sepsis models, pancreatitis, and ischemia-reperfusion injury, and inhibit the production of endotoxin-induced TNF in lung tissue. In addition, recent studies have demonstrated that GTS-21 inhibits the activities of endothelial cells and monocyte macrophages, as well as the secretion of pro-inflammatory cytokines in peripheral blood samples, by regulating the JAK2-STAT3 pathway. [1] in vivo: In septic animals, GTS-21 significantly ameliorated GI motility, lowered systemic and colonic levels of IL-6, decreased colonic permeability, and decreased the number of positive cultures obtained from blood and mesenteric lymph nodes. Splenectomy prevented animals from developing sepsis-induced ileus. Chrna7 mice displayed a more severe septic phenotype, whereas GTS-21 remarkably was also beneficial in these animals. [2]
αA-Conotoxin PIVA is a selective mouse musclenAChR inhibitor with IC50 for adult and fetal mouse musclenAChR sub> values are 2.3 nM and 22 nM respectively. αA-Conotoxin PIVA can be used in the study of neurological diseases.
Microgrewiapine A is an antagonist of nAChR. Microgrewiapine A inhibits hα4β2 and hα3β4 activity with 60% and 70% inhibition, respectively. Microgrewiapine A has selective cytotoxic against HT-29 human colon cancer cells with an IC50 of 6.8 μM[1].
Ropanicant (SUVN-911 free base) is a novel, potent, selective, and orally active neuronal nicotinic acetylcholine α4β2 receptor antagonist for the research of depression[1].
CCMI is a potent and selective α7 nAChR-positive allosteric modulator, does not bind to or activate α7 nAChRs via the orthosteric site, and causes significant positive modulation of agonist-induced currents at α7 nAChRs. CCMI has potential in CNS diseases with cognitive dysfunction[1].
Meclofenoxate hydrochloride, an ester of dimethylethanolamine (DMAE) and 4-chlorophenoxyacetic acid (pCPA), has been shown to improve memory, have a mentally stimulating effect, and improve general cognition.IC50 value: Target: nootropicMeclofenoxate, administered in a dose of 50 mg/kg twice daily for 7 days using the maze-training method, increased the number of responses to the conditioned stimulus, when retention tests were made 24 hours and 7 days after training, whereas citicholine, applied in the same way in a dose of 10 mg/kg, shortened the latency of the responses with reinforcement during the training and increased the number of correct responses to the conditioned stimulus in retention tests 7 days after the training [1]. Meclofenoxate appears to increase the consolidation of new information into long-term memory, but does not affect other aspects of remembering [2].
Adiphenine HCl is a nicotinic receptor inhibitor, used as an antispasmodic drug.Target: nAChRAdiphenine decreased the frequency of ACh-induced single-channel currents. adiphenine decreased cluster duration (36-fold at 100 micromolxL(-1)). adiphenine did not change amplitude but increased the decay rate (IC(50)= 15 micromolxL(-1)) [1]. Adiphenine was administered in3H-labelled form in doses of 15 u.mole/kg intravenously to male Wistar rats. Plasma and brain levels of the unchanged drug were measured [1]. The elimination of the3H -labelled compound from the plasma was monophasic with a half-life of 13 minutes. The unchanged drug was detectable in the plasma for 30 minutes after the injection. The time course of brain levels of unchanged drug paralleled that found in the plasma with a half-life of 9 to 12 minutes. In all experiments, brain and plasma levels of unchanged adiphenine correlate highly [2].
Rivanicline (RJR-2403) is a neuronal nicotinic receptor agonist, showing high selectivity for the α4β2 subtype (Ki=26 nM); > 1,000 fold selectivity than α7 receptors(Ki= 36000 nM).IC50 value: 26 nM [1]Target: α4β2 nAChRin vitro: At concentrations up to 1 mM, Rivanicline does not significantly activate nAChRs in PC12 cells, muscle type nAChRs or muscarinic receptors. Dose-response curves for agonist-induced ileum contraction indicate that Rivanicline is less than one-tenth as potent as nicotine with greatly reduced efficacy. Rivanicline does not antagonize nicotine-stimulated muscle or ganglionic nAChR function (IC50 > 1 mM). Chronic exposure of M10 cells to Rivanicline (10 microM) results in an up-regulation of high-affinity nAChRs phenomenologically similar to that seen with nicotine [1].in vivo: Rivanicline significantly improved passive avoidance retention after scopolamine-induced amnesia and enhanced both working and reference memory in rats with ibotenic acid lesions of the forebrain cholinergic projection system in an 8-arm radial maze paradigm. By comparison, Rivanicline was 15 to 30-fold less potent than nicotine in decreasing body temperature, respiration, Y-maze rears and crosses and acoustic startle response [2]. Metanicotine was about 5-fold less potent than nicotine in the tail-flick test after s.c administration, but slightly more potent after central administration [3].
N-Methylcytisine (Caulophylline), a tricyclic quinolizidine alkaloid, exerts hypoglycaemic, analgesic and anti-inflammatory activities. N-methylcytisine is a selective ligand of nicotinic receptors of acetylcholine in the central nervous system and has a high affinity (Kd = 50 nM) to nicotinic acetylcholine receptors (nAChR) from squid optical ganglia[1][2].
Nereistoxin (Nereistoxine) is a neurotoxin isolated from the marine annelid Lumbriconereis heteropoda that acts by blocking nicotinic acetylcholine receptors[1].
SUVN-911 is a potent, selective, brain penetrated and orally bioavailable neuronal nicotinic acetylcholine α4β2 receptor antagonist, with a Ki of 1.5 nM. SUVN-911 has antidepressant activity[1].
SSR180711 hydrochloride is an orally active, selective and reversible α7 acetylcholine nicotinic receptor (n-AChRs) partial agonist. SSR180711 hydrochloride can act on rat α7 n-AChR (Ki=22 nM; IC50=30 nM) and human α7 n-AChR (Ki=14 nM; IC50=18 nM). SSR180711 hydrochloride increases glutamatergic neurotransmission, ACh release and long-term potentiation (LTP) in the hippocampus[1].
D-Tubocurarine chloride pentahydrate is the chloride salt form of Tubocurarine, a nicotinic acetylcholine receptors (AChR) antagonist, and can be used as a skeletal muscle relaxant during surgery or mechanical ventilation. D-Tubocurarine chloride pentahydrate is also a potent neuromuscular blocking agent[1][2][3].
Nelonicline (ABT-126) is a selective neuronal nicotinic receptor agonist.
bPiDDB is a potent nAChR antagonist. bPiDDB potently (IC50=2 nM) inhibits nicotine-evoked striatal dopamine (DA) release through an interaction with α6β2-containing nAChRs[1].
Ispronicline (TC-1734), an orally active, brain-selective α4β2 nicotine acetylcholine receptor (nAChR) partial agonist, has shown memory-enhancing properties in rodents and a good tolerability profile. Ispronicline binds to the α4β2 nAChR with high affinity (Ki=11 nM) and is highly selective to other nAChRs such as α7 nAChR and α3β4 nAChR[1][2].
Nitenpyram is a calss of neonicotinoid and an insect nicotinic acetylcholine receptor (nAChR) agonist with an IC50 of 14 nM. Nitenpyram is an oral fast-acting insecticide used to suppress sucking insects on companion animals[1][2].