Tarafenacin(SVT-40776) is a highly selective M3 muscarinic receptor antagonist (Ki= 0.19 nM), ~200 fold selectivity over M2 receptor.IC50 value: 0.19 nM (Ki) [1]Target: M3 muscarinic receptorin vitro: SVT-40776 is highly selective for M(3) over M(2) receptors (Ki = 0.19 nmol.L(-1) for M(3) receptor affinity). SVT-40776 was the most potent in inhibiting carbachol-induced bladder contractions of the anti-cholinergic agents tested, without affecting atrial contractions over the same range of concentrations. SVT-40776 exhibited the highest urinary versus cardiac selectivity (199-fold) [1]. SVT-40776 has a much higher binding affinity (K(d) = 0.4 nM) to M5 mAChR than that of solifenacin (K(d) = 31 nM) with the same reeptor. The calculated binding free energy change (-2.3 ± 0.3 kcal/mol) from solifenacin to SVT-40776 is in good agreement with the experimentally derived binding free energy change (-2.58 kcal/mol), suggesting that our modeled M5 mAChR structure and its complexes with the antagonists are reliable [2].in vivo: In the guinea pig in vivo model, SVT-40776 inhibited 25% of spontaneous bladder contractions at a very low dose (6.97 microg.kg(-1) i.v), without affecting arterial blood pressure [1].
A-437203 is a selective D3 receptor antagonist with Ki of 71, 1.6, and 6220 nM for D2, D3, and D4 receptors, respectively.
D-Cycloserine is an analog of the amino acid D-alanine.Target: AntibacterialD-Cycloserine selectively potentiated the duration of motor cortical excitability enhancements induced by anodal tDCS. D-Cycloserine alone did not modulate excitability [1]. Participants receiving d-cycloserine in addition to exposure therapy reported significantly less social anxiety compared with patients receiving exposure therapy plus placebo. Controlled effect sizes were in the medium to large range [2]. Chronic D-cycloserine significantly reduced nicotine self-administration selectively in rats with low baseline nicotine use, but was ineffective with the rats with higher levels of baseline nicotine self-administration [3].
TCS1105 is a benzodiazepine ligand with agonist for α2-subunit containing GABAA receptors and antagonist for α1-subunit containing GABAA receptors. TCS1105 reduces anxiety-like behavior in mice. TCS1105 enhances offensive behavior and social dominance. TCS1105 blocks Sema3A induced AGC (axonal growth cones) collapse in a concentration-dependent fashion[1][2].
(E)-Ajoene is a oxygenated ajoene and organosulfur compound, which can be acquired via allicin decomposing. The polysulfides from garlic can be converted by human red blood cells into hydrogen sulfide (H2S) and allyl glutathione. (E)-Ajoene has been proved to show neuroprotective effects against ischemic damage. (E)-Ajoene is orally active to inhibit lipid peroxidation. (E)-Ajoene increases the number of cresyl violet-positive neurons and decreases the number of reactive gliosis in the CA1 region[1][2].
AMN082, a selective, orally active, and brain penetrant mGluR7 agonist, directly activates receptor signaling via an allosteric site in the transmembrane domain. AMN082 potently inhibits cAMP accumulation and stimulates GTPγS binding (EC50 values, 64-290 nM) at transfected mammalian cells expressing mGluR7. AMN082 shows selectivity over other mGluR subtypes and selected ionotropic glutamate receptors. Antidepressant effects[1][2].
AMG 333 is a potent and highly selective TRPM8 antagonist with an IC50 of 13 nM.
Gidazepam is an agonist of GABA receptor channels (GABA RCs).
QX-314 bromide is a membrane-impermeable permanently charged sodium channel blocker[1].
LY404039 is an inhibitor for mGluR1(Ki=149 nM) and mGluR2(Ki= 92 nM), which can also inhibit dopamine receptor.IC50 Value:149 nM(Ki for mGlu2); 92 nM(Ki for mGlu3)[1]Target: mGluR1; mGluR2Metabotropic glutamate (mGlu) receptors have been shown to mediate a number of behaviors including emotionality and responsivity to stress as demonstrated by efficacy in preclinical and clinical studies.in vitro: Similar to LY354740, LY404039 is a nanomolar potent agonist at recombinant human mGlu2 and mGlu3 receptors (K(i) = 149 and 92, respectively) and in rat neurons expressing native mGlu2/3 receptors (Ki = 88). LY404039 is highly selective for mGlu2/3 receptors, showing more than 100-fold selectivity for these receptors, versus ionotropic glutamate receptors, glutamate transporters, and other receptors targeted by known anxiolytic and antipsychotic medications[1].in vivo: LY404039 attenuated amphetamine- and phencyclidine-induced hyperlocomotion (3-30 and 10 mg/kg, respectively). LY404039 (3-10 mg/kg) inhibited conditioned avoidance responding. LY404039 also reduced fear-potentiated startle in rats (3-30 microg/kg) and marble burying in mice (3-10 mg/kg), indicating anxiolytic-like effects. Importantly, LY404039 did not produce sedative effects or motor impairment as measured by rotarod performance and lack of escape failures in the conditioned avoidance task (at doses up to 30 and 10 mg/kg, respectively). LY404039 (10 mg/kg) also increased dopamine and serotonin release/turnover in the prefrontal cortex [3].Clinical trial: An Absolute Bioavailability Study of LY-2140023 and LY-404039 in Healthy Subjects Using the Intravenous Tracer Method. Phage1
GV-196771A is the sodium salt form of GV196771, is an NMDA receptor antagonist.
Ondansetron-d3 (GR 38032-d3) hydrochloride) is the deuterium labeled Ondansetron hydrochloride. Ondansetron hydrochloride (GR 38032 hydrochloride) is a serotonin 5-HT3 receptor antagonist used mainly as anantiemetic (to treat nausea and vomiting), often following chemotherapy[1][2].
BDS-I known as blood depressing substance, is a marine toxin which can be extracted from Anemonia sulcata. BDS-I is a specific inhibitor of Potassium Channel, targeting to Kv3.4. BDS-I inhibits Aβ1-42-induced enhancement of KV3.4 activity, caspase-3 activation, and abnormal nuclear morphology of NGF-differentiated PC-12 cells. BDS-I reverts the Aβ peptide-induced cell death[1].
Risperidone E-oxime is an impurity of Risperidone[1]. Risperidone is a serotonin 5-HT2 receptor blocker, P-Glycoprotein inhibitor and potent dopamine D2 receptor antagonist, with Kis of 4.8, 5.9 nM for 5-HT2A and dopamine D2 receptor, respectively [2][3].
Proflavine, an acridine dye, is a known DNA intercalating agent. Anti-microbial agent[1]. Proflavine behaves as a pore blocker for Kir3.2. Proflavine is a potential lead compound for Kir3.2-associated neurological diseases[2].
Gluco-obtusin is an anthraquinone. Gluco-obtusin can be isolated from the seeds of Cassia obtusifolia[1].
Citrinin is a mycotoxin which causes contamination in the food and is associated with different toxic effects. Citrinin is usually found together with another nephrotoxic mycotoxin, Ochratoxin A. Citrinin is also reported to possess a broad spectrum of bioactivities, including antibacterial, antifungal, and potential anticancer and neuro-protective effects in vitro[1][2].
1-(Anilinocarbonyl)proline can be used to identify dual action probes in a cell model of Huntington[1].
KSC-34 (PDIA1 inhibitor KSC-34) is a potent, selective protein disulfide isomerase A1 (PDIA1) inhibitor, 30-fold selectivity for the A-site over the A' site; displays time-dependent inhibition of PDIA1 reductase activity in vitro with a kinact/ KI of 9.66 × 103 M-1 s-1 and is selective for PDIA1 over other members of the PDI family, and other cellular cysteine-containing proteins; significantly decreases the rate of secretion of a destabilized, amyloidogenic antibody light chain, thereby minimizing pathogenic amyloidogenic extracellular proteins in treated cells.
Glutaminyl Cyclase Inhibitor 2 is a glutaminyl cyclase inhibitor with an IC50 of 1.23 μM.
Ripasudil (K-115) is a specific inhibitor of ROCK, with IC50s of 19 and 51 nM for ROCK2 and ROCK1, respectively.
Bencianol is a the semisynthetic flavinoid, with anti-spasmogenic activities.
Valnoctamide-d5 (Valmethamide-d5) is the deuterium labeled Valnoctamide. Valnoctamide (Valmethamide), a derivative of valproate, suppresses benzodiazepine-refractory status epilepticus. Valnoctamide (Valmethamide) acts directly on GABAA receptors[1][2].
β-Amyloid precursor protein (96-110), cyclized (human) is an amyloid precursor protein. β-Amyloid precursor protein (96-110), cyclized (human) can be used in study Alzheimer’s disease[1].
MLGFFQQPKPR-NH2 is a reversed Substance P peptide. Substance P is a neuropeptide[1].
Droxidopa (L-DOPS) hydrochloride is a potent, orally active norepinephrine precursor. Droxidopa hydrochloride increases standing blood pressure, ameliorates symptoms of orthostatic hypotension and improves standing ability. Droxidopa hydrochloride has the potential for the research of neurogenic orthostatic hypotension (nOH) and alternative ADHD (attention deficit hyperactivity disorder)[1][2][3][4].
PACAP (1-27), human, ovine, rat, the N-terminal fragment of PACAP-38, is a potent PACAP receptor antagonist with IC50s of 3, 2, and 5 nM, respectively, for rat PAC1, rat VPAC1, and human VPAC2.
LY-281217 is a potent mu-opioid agonist with analgesic effects[1].
[D-Ala2]-GIP (human) is a GIP receptor agonist. [D-Ala2]-GIP (human) improves glucose tolerance. [D-Ala2]-GIP (human) shows neuroprotective activity in MPTP-induced Parkinson's disease model. [D-Ala2]-GIP (human) also improves cognitive function and hippocampal synaptic plasticity in obese diabetic rats. [D-Ala2]-GIP (human) can be used for research of type 2 diabetes, Parkinson's disease, etc[1]