Epiberberine is an alkaloid isolated from Coptis chinensis, acts as a potent AChE and BChE inhibitor, and a non-competitive BACE1 inhibitor, with IC50s of 1.07, 6.03 and 8.55 μM, respectively. Epiberberine has antioxidant activity, with peroxynitrite ONOO- scavenging effect (IC50, 16.83 μM), and may protect against Alzheimer disease[1]. Epiberberine inhibits the early stage of differentiation of 3T3-L1 preadipocytes, downregulates the Raf/MEK1/2/ERK1/2 and AMPKα/Akt pathways[2]. Epiberberine has the potential effect in the research of diabetic disease[3].
Cyclothiazide, a positive allosteric modulator of AMPA receptors, is used frequently to block the desensitization of both native and heterologously expressed AMPA receptors. Cyclothiazide is known to produce a fast inhibition of AMPA receptor desensitization and a much slower potentiation of the AMPA current[1].
Mesembrine ((+)-Mesembrine) a main alkaloid that features an aryloctahydroindole skeleton. Mesembrine is a 5-HT transporter inhibitor with a Ki of 1.4 nM. Mesembrine also inhibits phosphodiesterase 4B (PDE4B) with an IC50 of 7.8 μM[1][2].
MLS1547 is a highly efficacious G protein-biased dopamine D2 receptor (D2R) agonist (Ki=1.2 μM). MLS1547 stimulates D2R G protein-mediated signaling (EC50=0.37 μM in a calcium mobilization assay). MLS1547 acts as an antagonist for dopamine (DA)-stimulated β-arrestin recruitment to the D2R (IC50=9.9 μM)[1][2].
[Nphe1]Nociceptin(1-13)NH2, a novel nociceptin/orphanin FQ (NC) endogenous ligand, is a selective and competitive ociceptin receptor antagonist without any residual agonist activity. [Nphe1]nociceptin(1-13)NH2 binds selectively to recombinant nociceptin receptors (pKi=8.4) and antagonizes the inhibitory effects of nociceptin on cyclic AMP accumulation in CHO cells (pA2=6.0). [Nphe1]Nociceptin(1-13)NH2 has the potential to act as an analgesic agent[1].
Arecaidine hydrobromide, a pyridine alkaloid, is a potent GABA uptake inhibitor. Arecaidine hydrobromide is a substrate of H+-coupled amino acid transporter 1 (PAT1, SLC36A1) and competitively inhibits L-proline uptake[1][2].
Pramipexole-d7-1 (dihydrochloride) is the deuterium labeled Pramipexole dihydrochloride[1]. Pramipexole dihydrochloride is a selective and blood-brain barrier (BBB) penetrant dopamine D2-type receptor agonist, with Kis of 2.2 nM, 3.9 nM, 0.5 nM and 1.3 nM for D2-type receptor, D2, D3 and D4 receptors, respectively. Pramipexole dihydrochloride can be used for the research of Parkinson's disease (PD) and restless legs syndrome (RLS)[2][3][4].
SB 243213 dihydrochloride is an orally active, selective and high-affinity 5-hydroxytryptamine (5-HT)2C receptor antagonist with a pKi of 9.37 and a pKb of 9.8 for human 5-HT2C receptor. SB 243213 dihydrochloride has improved anxiolytic profile and has the potential for schizophrenia and motor disorders[1].
α7 Nicotinic receptor agonist-1 (Preparation 5) is an α7 nAChR agonist. α7 Nicotinic receptor agonist-1 can be used in studies of psychiatric disorders (such as schizophrenia, manic or hypomanic depression and anxiety disorders) and intellectual disorders (such as alzheimer's disease, learning deficits, cognitive deficits, attention deficits, memory loss, lewy body dementia and attention deficit hyperactivity disorder)[1].
4-PPBP maleate is a potent σ 1 receptor ligand and agonist. 4-PPBP maleate is a non-competitive, selective NR1a/2B NMDA receptors (expressed in Xenopus oocytes) antagonist. 4-PPBP maleate provides neuroprotection[1][2][3].
Rispenzepine is a novel antimuscarinic compound with a preferential action at M1, and M3 receptor subtypes.
Sertindole, a neuroleptic, is one of the newer antipsychotic medications available.Target: Multi-targetIn vitro studies showed that sertindole exerts a potent antagonism at serotonin 5-HT2A, 5-HT2C, dopamine D2, and αl adrenergic receptors. Sertindole offers an alternative treatment option for refractory patients given its good EPS profile, favorable metabolic profile, and comparable efficacy to risperidone. Due to cardiovascular safety concerns, sertindole is available as a second-line choice for patients intolerant to other antipsychotic agents [1]. Sertindole should prove to be a very useful addition to the therapeutic options available for the treatment of psychotic disorders [2]. Sertindole improves negative symptoms, and is also effective for the treatment of neuroleptic-resistant schizophrenia. Sertindole is generally well tolerated and is associated with a low rate of extrapyramidal symptoms (EPS). Thus, sertindole is a useful option in the treatment of patients with schizophrenia [3].
Ethopropazine (Isothazine) hydrochloride is a potent, selective BChE inhibitor and a poor AChE inhibitor. Ethopropazine hydrochloride is a phenothiazine compound with anticholinergic properties. Ethopropazine hydrochloride can be used for the research of Parkinson’s disease[1][2].
AVN-492 is a very specific and highly-selective antagonist with picomolar affinity to 5-HT6R (Ki=91 pM).
(R)-Oxybutynin hydrochloride, a (R)-isomer of Oxybutynin hydrochloride, is an orally active muscarinic receptor antagonist. (R)-Oxybutynin hydrochloride has antimuscarinic, antispasmodic and anticholinergic activity, competitively antagonizes Carbachol-induced contractions. (R)-Oxybutynin hydrochloride can be used for researching incontinence due to neurogenic bladder dysfunction[1][2][3].
Donepezil(E 2020) is a specific and potent AChE inhibitor for bAChE and hAChE with IC50 of 8.12 nM and 11.6 nM, respectively.Target: AChEDonepezil is a specific and potent AChE inhibitor for bAChE and hAChE with IC50 of 8.12 nM and 11.6 nM , respectively [1]. Donepezil inhibits the carbachol-stimulated increase in intracellular Ca2+ concentration in human SHSY5Y neuroblastoma cells in a concentration dependent manner, indicating that Donepezil have muscarinic antagonist activity. Intraperitoneal administration of Donepezil in rats produces a dose dependent increase in salivation and tremor, which are overt cholinergic behavioural signs, with an ED50 of 6 μmol/kg. Donepezil is found to be somewhat less potent with a ED50 of 50 μmol/kg following oral administration [2]. A recent study shows that Donepezil can protect human umbilical vein endothelial cells (HUVECs) against H2O2-induced cell injury. This may be useful as a potential therapy for oxidative stress in cardiovascular and cerebrovascular diseases [3].
A small molecule 5-HT1A and 5-HT2A receptor antagonist and inhibitor of serotonin and dopamine reuptake, also possess affinity for the α1A- and α1B-adrenergic receptors. Depression Phase 2 Clinical
Perospirone (SM-9018 free base) is an orally active antagonist of 5-HT2A receptor (Ki=0.6 nM) and dopamine D2 receptor (Ki=1.4 nM), and also a partial agonist of 5-HT1A receptor (Ki=2.9 nM). Perospirone is an atypical antipsychotic drug and has the potential for schizophrenic disease[1][2].
Vazegepant (BHV-3500) hydrochloride is a highly affinity CGRP receptor antagonist (hCGRP Ki= 0.023 nM). Vazegepant hydrochloride is the first intranasal gepant for migraine. Vazegepant hydrochloride may be helpful in effective management of COVID-19 associated pulmonary inflammation[1][2][3].
Kynuramine (dihydrobromide), an endogenously occurring amine, is a fluorescent substrate and probe of plasma amine oxidase[1][2].
Rizatriptan-d6 benzoate (MK 462-d6) is the deuterium labeled Rizatriptan benzoate. Rizatriptan benzoate is a 5-HT1 agonist triptan drug for the treatment of migraine headaches[1][2].
5-HT1A modulator 2 hydrochloride, a derivative of 8-OH-DPAT (HY-112061), is a modulator of 5-HT1A with a Ki of 53 nM for 5-HT1A binding[1].
Mirtazapine is a potent tetracyclic antidepressant.Target: 5-HT ReceptorMirtazapine, the novel antidepressant, has a dual mode of action. It is a noradrenergic and specific serotonergic antidepressant (NaSSA) that acts by antagonizing the adrenergic alpha2-autoreceptors and alpha2-heteroreceptors as well as by blocking 5-HT2 and 5-HT3 receptors [1].Mirtazapine appears to have a substantial ameliorating effect on hot flushes and perspiration bouts. It is postulated that the 5-HT(2A) blocking properties of mirtazapine is accounted in the symptomatic relief of hot flushes [2]. After 4-24 weeks of treatment, mirtazapine induced downregulation of platelet alpha(2A)-adrenoceptors (up to 34%) and Galphai proteins (up to 28%), and the upregulation of GRK 2 (up to 30%). Treatment with mirtazapine reversed this abnormality and induced downregulation of alpha(2A)-adrenoceptor/Galphai complex [3].
LY450108 is an alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor potentiator. IC50 value: Target: AMPA receptors mediate most of the excitatory neurotransmission and play a key role in synaptic plasticity in the mammalian central nervous system (CNS). Recent evidence has shown that in addition to modulating fast synaptic plasticity and memory processes, AMPA receptor potentiators alter downstream signalling pathways and may thereby have utility in other CNS disorders.
Ph-HTBA is a high-affinity, brain-penetrating modulator for CaMKIIα. Ph-HTBA has binding affinity for CaMKIIα with a Kd value of 757 nM. Ph-HTBA can be used for the research of ischemia and neurodegenerative disorders[1].
Calmodulin-Dependent Protein Kinase II (290-309) is a potent CaMK antagonist with an IC50 of 52 nM for inhibition of Ca2+/calmodulin-dependent protein kinase II.
Iproniazid is a non-selective, irreversible monoamine oxidase (MAO) inhibitor of the hydrazine class. Iproniazid has antidepressive activity[1].
Topiramate D12 (McN 4853 D12) is a deuterium labeled Topiramate. Topiramate is a broad-spectrum antiepileptic agent. Topiramate is a GluR5 receptor antagonist. Topiramate produces its antiepileptic effects through enhancement of GABAergic activity, inhibition of kainate/AMPA receptors, inhibition of voltage-sensitive sodium and calcium channels, increases in potassium conductance, and inhibition of carbonic anhydrase[1][2][3].
Novel fluorescent substrate for both the serotonin transporter and the vesicular monoamine transporter 2 (VMAT2)