Neuroscienza

Dothiepin (Dosulepin; Dothep), an antidepressant with sedative/anxiolytic properties, preferentially inhibits noradrenaline over serotonin uptake, enhancing

ABT-418 HCl enhances cognition and reduces anxiety as a selective nAChRs agonist, researched for Alzheimer's.

Lanabecestat (AZD3293/LY3314814) is a potent oral BACE1 inhibitor that crosses the BBB and reduces Aβ levels.

PZ-1190, a multitarget ligand for serotonin and dopamine receptors, exhibits potential antipsychotic activity in rodents [1].

GR 125487 sulfamate is a 5-HT4 receptor antagonist.

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.

Fosthiazate is a broad-spectrum nematicide that combats a range of plant parasitic nematodes such as Meloidogyne spp., Globodera spp., and Pratylenchus spp., by

MRK-560 is an effective and brain-penetrant inhibitor of γ-secretase.

SCS is a GABAA receptor antagonist.

4-Chloro-L-phenalanine (L-PCPA) is an inhibitor of 5-HT biosynthesis and a non-specific antagonist of tryptophan hydroxylases (TPH1 and TPH2).

Org-21465, a gamma-aminobutyric acid (GABA) receptor agonist, is used potentially for the use of anesthesia.

AAK1-IN-3: Brain-penetrant AAK1 inhibitor for neuropathic pain research; IC50=11 nM.

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

PNU109291, a potent and selective agonist of the 5-HT1D receptor, effectively mitigates dural plasma extravasation induced by trigeminal ganglion stimulation.

CGP 54626 hydrochloride is a GABAB receptor antagonist.

AChE-IN-31 (compound 1), a non-competitive acetylcholinesterase (AChE) inhibitor, exhibits potential for Alzheimer's disease research [1].

JM-1232 is a sedative and hypnotic drug being researched as a potential anesthetic.

Biphenylindanone A is a selective potentiator of human mGluR2 (hmGluR2),and for the treatment of neurological disorders.

Robalzotan is a selective 5-HT1A receptor antagonist.

VU0360172 is a positive allosteric modulator of mGlu5 receptors (EC50 = 16 nM; Ki = 195 nM).

TPA 023 is a selective agonist of GABAA α2/α3 subtype (Kis = 0.19 - 0.41 nM).

L 663581 is the benzodiazepine receptor partial agonist.

MAO-B-IN-27 (Compound 12c), a monoamine oxidase B (MAO-B) inhibitor, exhibits a potent and selective inhibitory effect on hMAO-B, with an IC50 value of 8.9 nM,

Brasofensine sulfate is a dopamine reuptake inhibitor.

L 687306 is a partial agonist of muscarinic M1 receptors. It is also a highly competitive antagonist at cardiac M2 receptors and ileal M3 muscarinic receptors.

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

Piperidine-4-sulfonic acid is a potent GABA agonist, demonstrating an IC50 value of 0.034 μM for the inhibition of H-GABA binding [1].

Antioxidant agent-15 (Compound 4) demonstrates potent antioxidant inhibition activity, exhibiting an IC50 value of 15.44 nM.

BACE-1 inhibitor 1 (Compound 8a) is an effective BACE-1 inhibitor (IC50: 56 nM).

Zaldaride (free base) is a calmodulin antagonist.

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.

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

GSM-1 is a modulator of γ-Secretase.

Hydroxy varenicline, a metabolite of the nicotinic acetylcholine receptor (nAChR) agonist varenicline, functions within the biochemical pathway by interacting with nAChR sites.

mGAT3/4-IN-2 are potent inhibitors of mGAT3/mGAT4 with their pIC50 values of 5.44 and 5.25, respectively.

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.

Cyclophostin is an irreversible inhibitor of acetylcholinesterase (AChE).

Mesembrine is an alkaloid, a 5-HT transporter inhibitor (K i 1.4 nM), and inhibits PDE4B (IC50 7.8 μM).

Octahydroaminoacridine succinate, an acetylcholinesterase inhibitor, is used potentially for the treatment of Alzheimer's disease.

VU6007477 is a brain-penetrant M1 muscarinic receptor PAM (EC50 230 nM) used for research on CNS exposure and seizure-related models.

Indeloxazine HCl: Serotonin releaser, NE reuptake inhibitor, NMDA antagonist; antidepressant that boosts acetylcholine in rats.

CGP-54626 is a selective antagonist of the GABAB receptor (IC50 = 4 nM ).

AAK1-IN-5: Potent, selective AAK1 inhibitor; CNS-penetrant; oral; IC50: 1.2 nM; Ki: 0.05 nM; cell IC50: 0.5 nM. Useful in neuropathic pain research.

Quinolactacin A1, a strong AChE inhibitor from Penicillium citrinum, aids Alzheimer's research.

Facinicline hydrochloride (RG3487) is both a novel nicotinic alpha-7 receptor (alpha7nAChR) partial agonist (Ki = 6 nM) and an antagonist of 5-HT3(Ki = 1.2 nM).

VU6012962 is an orally bioavailable negative allosteric modulator of CNS-penetrant metabotropic glutamate receptor 7(mGlu7; IC50: 347 nM).

AChE-IN-30 is an acetylcholinesterase inhibitor (IC50 4.4 μM) that reduces oxidative stress and apoptosis, useful for Alzheimer’s disease research models.

5-HT3 antagonist 1 is a potent and selective antagonist of 5-HT3 receptor.

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

Gentisein (NSC-329491), a primary metabolite of Mangiferin, exhibits significant inhibition of serotonin uptake, demonstrating potency with an IC50 value of 4.7

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

LY2033298 enhances oximoline's effect on hamster circadian rhythms, aiding neurosystem disorders.

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.

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

Frovatriptan, potent 5-HT 1B/D agonist, shows high cerebroselectivity and efficacy for migraine with aura.

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].

RPC425 is a noncompetitive inhibitors of the Betaine-γ-Aminobutyric Acid Transporter 1 (BGT1).

Anti-amyloid agent-1 is a potent compound that inhibits amyloid aggregation, offering a promising approach for research into the treatment of amyloidosis [1].

Flesinoxan HCl is the salt form of Flesinoxan, which is a selective 5-HT1A receptor agonist.

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

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

(2R,4R)-APDC is a selective group II metabotropic glutamate receptors (mGluRs) agonist. It has anticonvulsant and neuroprotective effects.

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

ELND007 is a Gamma secretase inhibitor.

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

rTRD01 is a TDP-43 ligand that selectively binds to the RRM1 and RRM2 domains of TDP-43, exhibiting a dissociation constant (Kd) of 89 µM for TDP-43 102–269.

2-Methyl-5-HT (2-Methyl-5-hydroxytryptamine) is a potent and selective 5-HT3 receptor agonist with anti-depressive-like effects.

U 89843A is a positive allosteric modulator of gamma-aminobutyric acid (GABA)A receptors.

MAO-B-IN-1 is a monoamine oxidase B inhibitor and can be used for the research of neurological diseases.

Rel-HDMP-28 hydrochloride (Compound 2g) is an analogue of methylphenidate, exhibiting selective affinity for the serotonin transporter (SERT) with a binding constant (Ki) of 105 nM [1].

Compound 4a, a mAChR antagonist, exhibits K i values of 255 nM for M1 and M5 subtypes, and lower values of 121 nM and 158 nM for M3 and M4 subtypes,

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

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

GYKI-46903 is a noncompetitive 5-HT3 receptor antagonist.

KBR 2822 is an inhibitor of esterase.

Butriptyline (Butriptylene), a tricyclic antidepressant, is effective when administered orally [1].

BACE1-IN-1 is a high brain penetrant BACE1 inhibitor (IC50s: 32 and 47 nM for human BACE1 and BACE2).

L-772,405 is a highly selective agonists of h5-HT(1D) receptor.

Adenylyl cyclase-IN-1 is a potential adenylyl cyclase inhibitor for ocular hypotonia research [1].

BMT-124110: AAK1 inhibitor, IC50=0.9 nM, pain relief. BMT-090605: BIKE inhibitor, IC50=17 nM; GAK inhibitor, IC50=99 nM.

"(1R,4R)-N-desmethyl Sertraline, a metabolite of the selective serotonin reuptake inhibitor (SSRI) sertraline, plays a key role in its pharmacological effects."

rat 5-HT1B receptor antagonist

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

cholinesterase inhibitor

Bexicaserin (Compound 3), a 5-HT2C receptor agonist, has potential applications in research pertaining to obesity and psychiatric disorders [1].

NO-711ME (N-O711 Methyl ester) is a prodrug of NO-711. It also is a potent and selective GABA uptake inhibitor.

Velusetrag(TD-5108), a potent 5-HT4 agonist, is in development for gastroparesis, constipation, and IBS.