Neuroscience

UNC9994 hydrochloride is a selective β-arrestin-biased D2R agonist, Ki of 79 nM, that stimulates β-arrestin and modulates cAMP.

QM-FN-SO3 is a blood-brain barrier (BBB)-penetrable, near-infrared (NIR) probe with aggregation-induced emission (AIE) activity, specifically designed for the detection of Aβ plaques. It exhibits ultra-high signal-to-noise (S/N) ratio, binding affinity, and high-performance NIR emission, making it suitable for in vivo detection of Aβ plaques [1].

C3 functions as a selective inhibitor of monoamine oxidase B (MAO-B; IC50= 0.021 µM), demonstrating preference over monoamine oxidase A (MAO-A; IC50= 26.8 µM). This compound, at dosages of 0.1, 1, and 3 mg/kg, effectively counters MPTP-induced reductions in dopamine levels within the mouse brain.

1-Carboxycyclohexaneacetic acid may be present as a potential impurity in commercial gabapentin, an antiepileptic drug. Furthermore, it serves as a precursor for synthesizing antagonists targeting the serotonin (5-HT) receptor subtype 5-HT2A.

MAO-B-IN-13: a potent, reversible MAO-B inhibitor with BBB penetration, neuroprotective effects; used in Parkinson’s research (IC50=10nM).

GMA-839 is a selective modulator of gamma-aminobutyric acid(A) receptors.

R-96544 is an orally active antagonist of the 5-HT2A receptor that has demonstrated the ability to inhibit platelet aggregation in vitro [1].

AMG-8718, an oral BACE1 blocker (IC50: 0.0007 μM), also inhibits BACE2 (IC50: 0.005 μM), lowering CSF and Aβ40 brain levels.

Gepirone is a 5-HT1A receptor agonist belonging to the buspirone family. Gepirone HCl possesses greater selectivity for the 5-HT1A receptor than SSRIs.

L-APB is an effective and specific agonist for the group III mGluRs (EC50s: 0.13, 0.29, 1.0, 249 μM for mGlu4, mGlu8, mGlu6, and mGlu7 receptors, respectively).

2-Aminotetralin acts as a neuromodulatory agent by inhibiting serotonin (5-HT) and norepinephrine reuptake in the rat brain at a dose of 39.4 mg/kg. It triggers hypothermia in rats through intracisternal or intraperitoneal injection, while the implantation of crystals in the hypothalamus' medial preoptic area leads to hyperthermia. Additionally, it mimics (+)-amphetamine in a two-lever drug discrimination test among rats in a dose-dependent manner.

Nemonapride is a dopamine D2-like receptor antagonist.

Cyanopindolol fumarate is a 5-HT receptor antagonist [1].

Wf-516 is a 5-HT reuptake inhibitor (Kis: 5 nM and 40 nM for 5-HT1A receptor and 5-HT2A receptor in humans, respectively), and with potent antidepressant

AMPA receptor modulator-6, an AMPA receptor positive allosteric modulator (PAM), is utilized in the research of neurological diseases [1].

mGluR5 antagonist-1 (compound 10) is a potent mGluR5 inhibitor exhibiting an IC50 of 11.5 nM and demonstrates antidepressant effects [1].

Lanabecestat camsylate is used as a BACE1 Inhibitor.

13,14-dihydro-15-keto Prostaglandin E2 (13,14-dihydro-15-keto PGE2) serves as the predominant metabolite of PGE2 in plasma, created through a 15-keto PGE2 intermediate by the action of 15-oxo-PG Δ13 reductase. Unlike its precursor PGE2, this compound exhibits poor binding affinity towards EP2 and EP4 PGE2 receptors (Ki values of 12 and 57 µM, respectively) in CHO cells and fails to stimulate adenylate cyclase activity therein (EC50s >18 and >38 µM, respectively). Concentrations of 13,14-dihydro-15-keto PGE2 are notably higher in the plasma of pregnant women during their third trimester and at labor and delivery stages, whereas its levels are found to be reduced in the tumor tissues of patients with non-small cell lung cancer (NSCLC) compared to adjacent healthy tissue.

PQM130 is a Feruloyl-Donepezil Hybrid compound against the neurotoxicity induced by Aβ1-42 oligomer (AβO) and shows anti-inflammatory activity.

Robalzotan is a selective 5-HT1A receptor antagonist.

GR-127935 is a potent and selective 5-HT1B/1D receptor antagonist.

CGP36216 hydrochloride acts as a selective antagonist at the presynaptic GABA receptor, specifically binding to the GABAB receptor with a Ki value of 0.3 μM. This compound is leveraged in research focused on anxiety and trauma-related disorders [1] [2].

cholinesterase inhibitor

LY-426965 is a selective, potent, orally bioavailable 5-HT1A antagonist.

AChE-IN-30 is an acetylcholinesterase (AChE) inhibitor exhibiting neuroprotective effects with an inhibitory concentration (IC 50) of 4.4 μM.

5-HT3-In-1 (compound example 8) exhabits with 5-HT3 inhibition activity.

AAK1-IN-2, a potent (IC50=5.8 nM) AAK1 inhibitor, selective & brain-penetrant, is used for neuropathic pain studies.

CGP 55845: potent, selective GABAB blocker, IC50=5 nM, hinders agonist binding, reduces GABA/glutamate release.

SB 649915 is a serotonin reuptake inhibitor and 5-HT1A and 5-HT1B receptor antagonist.

Brasofensine, a benztoalkane MA reuptake inhibitor, shows promise for Parkinson's and Alzheimer's.

GABA-IN-2 (Compound 5), a GABA inhibitor, exhibits both larvicidal and insecticidal properties, achieving an 87% mortality rate at a concentration of 50 mg/L [1

BChE-IN-20 (compound 7c) is a potent, selective inhibitor of BChE, demonstrating IC50 values of 105 nM for eqBChE and 2.3 nM for hBChE.

QR-0217 is a potent inhibitor of both Aβ1-40 and α-synuclein aggregation, exhibiting an IC50 of 7.5 µM for Aβ1-40.

3β-Hydroxy-lup-20(29)-en-16-one (compound 9) serves as a dual inhibitor of both AChE and BChE, displaying a preference for BChE with an IC50 of 28.9 μM [1].

LY2140023 hydrochloride: oral methionine prodrug of LY404039, a selective mGlu2/3 agonist, studied for schizophrenia.

eeAChE-IN-2 is a potent inhibitor of eeAChE, exhibiting inhibitory potency with an IC50 of 2 nM.

JNJ-46281222: mGlu2-selective, potent PAM, Kd = 1.7 nM, pEC50 = 7.71.

Lanabecestat (AZD3293) is a BACE1 inhibitor (Ki: 0.4 nM), Lanabecestat is used in the study of neurological diseases like Alzheimer's disease.

Diproqualone, analogous to methaqualone, exhibits sedative, anxiolytic, anti-inflammatory, and analgesic properties [1].

1CAY10649, a thiazolinone compound, directly inhibits 5-lipoxygenase (5-LO) product formation in intact polymorphonuclear leukocytes (PMNL) with an IC50 value of 0.28 μM and in a soluble fraction of an S100 PMNL cell lysate with an IC50 value of 0.09 μM, following stimulation by calcium and arachidonic acid. This activity highlights its potential in mitigating inflammatory responses by targeting the biosynthesis of leukotrienes, substances implicated in various inflammatory processes such as neutrophil chemotaxis, increased vascular permeability, and smooth muscle contraction.

(S)-Renzapride (BRL 24924), 5-HT4 agonist (Ki 115 nM), 5HT2b/5HT3 antagonist, for C-IBS study.

(R)-4-Amino-3-hydroxybutyric acid, also known as (R)-GABOB, acts as a modulator of GABA receptors, specifically binding to both GABAA and GABAB receptors and blocking GABA reuptake in rat brain synaptosomes. Additionally, it serves as a GABAC receptor agonist, triggering currents in patch-clamp assays with Xenopus oocytes that express the human receptor. In vivo studies reveal its capability to suppress electrical discharges in the amygdala in cats undergoing N-amidinobenzamide-triggered seizures, indicating its potential therapeutic application in managing seizure disorders.

MGS-0039: Group II mGluR2/3 antagonist, non-serotonergic antidepressant-like effect, AMPA involvement, regulates dopamine in NAc.

Brasofensine Maleate inhibits the monoamine re-uptake.

Serine Hydrolase Inhibitor-21 (compound 8), a pyridine-based serine hydrolase inhibitor, exhibits a K i of 429 nM against BuChE, and shows promise for Alzheimer

(±)-N-desmethyl Venlafaxine, a minor active metabolite of venlafaxine, serves as a selective norepinephrine and serotonin reuptake inhibitor (SNRI). Generated through the metabolization by the cytochrome P450 (CYP) isoform CYP3A4, it exhibits reuptake inhibition of norepinephrine and serotonin in rat synaptosome preparations, demonstrated by IC50 values of 4.7 and 1.6 µM, respectively. Clinically, it has been shown to counteract reserpine-induced hypothermia in mice, displaying efficacy at a minimum effective dose (MED) of 10 mg/kg.

MFZ 10-7 is anegative allosteric modulator of the mGluR5.

rat 5-HT1B receptor antagonist