Virodhamine is an endocannabinoid, it regulates neurotransmission by activating the cannabinoid (CB) receptors. Virodhamine is an antagonist of CB1 receptor and an agonist of CB2 receptor. Virodhamine induces megakaryocytic differentiation by triggering MAPK signaling and ROS production. Virodhamine can be used for the research of various neurological disorders such as Alzheimer's and Parkinson's diseases[1][2].
Moringin is a potent and selective TRPA1 ion channel natural agonist with an EC50 of 3.14 μM. Moringin does not activate or activates very weakly the vanilloids somatosensory channels TRPV1, TRPV2, TRPV3 and TRPV4, and the melastatin cooling receptor TRPM8. Moringin has hypoglycemic, antimicrobial, anti-inflammatory, anticancer and neuroprotection activities[1][2].
Pilocarpine Hydrochloride is a selective M3-type muscarinic acetylcholine receptor (M3 muscarinic receptor) agonist.
Naratriptan is a selective 5-HT1 receptor subtype agonist and is a triptan drug that is used for the treatment of migraine headaches.Target: 5-HT1 ReceptorNaratriptan is a triptan drug marketed by GlaxoSmithKline and is used for the treatment of migraine headaches. Naratriptan is available in 2.5 mg tablets. It is a selective 5-HT1 receptor subtype agonist. Naratriptan is used for the treatment of the acute migraine attacks and the symptoms of migraine, including severe, throbbing headaches that sometimes are accompanied by nausea and sensitivity to sound or light.The causes of migraine are not clearly understood; however, the efficacy of naratriptans and other triptans is believed to be due to their activity as 5HT (serotonin) agonists.A meta-analysis of 53 clinical trials has shown that all triptans are effective for treating migraine at marketed doses and that naratriptan, although less effective than sumatriptan and rizatriptan was more effective than placebo in reducing migraine symptoms at two hours and efficacy was demonstrated in almost two thirds of subjects after four hours of treatment.
7-Hydroxyquetiapine (ICI 214227) is the major active metabolite of antipsychotic medicine Quetiapine[1].
Clocapramine hydrochloride hydrate is an antagonist of the D2 and 5-HT2A receptors.
Lurasidone is an antagonist of both dopamine D2 and 5-HT7 with IC50s of 1.68 and 0.495 nM, respectively. Lurasidone is also a partial agonist of 5-HT1A receptor with an IC50 of 6.75 nM.
Amitriptyline Hydrochloride is a dibenzocycloheptene-derivative tricyclic antidepressant (TCA).Target: OthersAmitriptyline acts primarily as a serotonin-norepinephrine reuptake inhibitor, with strong actions on the serotonin transporter and moderate effects on the norepinephrine transporter. It has negligible influence on the dopamine transporter and therefore does not affect dopamine reuptake, being nearly 1,000 times weaker on it than on serotonin [1]. Amitriptyline additionally functions as a 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, α1-adrenergic, H1, H2, and mACh receptorantagonist, and σ1 receptor agonist. It has also been shown to be a relatively weak NMDA receptor negative allosteric modulator at the same binding site as phencyclidine. Amitriptyline inhibits sodium channels, L-type calcium channels, and Kv1.1, Kv7.2, and Kv7.3 voltage-gated potassium channels, and therefore acts as a sodium, calcium, and potassium channel blocker as well [2]. Recently, amitriptyline has been demonstrated to act as an agonist of the TrkA and TrkB receptors. It promotes the heterodimerization of these proteins in the absence of NGF and has potent neurotrophic activity both in-vivo and in-vitro in mouse models [3].
JZL195 is a selective and efficacious dual FAAH/MAGL inhibitor with IC50 of 13 nM and 19 nM for mouse brain FAAH and MAGL respectively.IC50 value: 13 nM/19 nM (mouse brain FAAH/MAGL) [1]Target: dual FAAH/MAGL inhibitorin vitro: JZL195 shows only modest and incomplete inhibitory activity against NTE (IC50 >5 uM). At higher concentrations, JZL195 inhibited ABHD6 but not any of the other brain serine hydrolases detected in our competitive ABPP assays. JZL195 also inhibited rat and human FAAH and MAGL enzymes with IC50 values in the range of 10–100 nM based on competitive ABPP assays [1].in vivo: A time course analysis of mice given one administration ofJZL195 (20 mg/kg, i.p.) revealed that blockade of FAAH andMAGL lasted at least 10 h as judged by gel-based ABPP or AEAand 2-AG hydrolysis assays [1]. The effect of systemic injections of a range of doses of JZL195 and the pan-cannabinoid receptor agonist WIN55212 were performed 1 day following intraplantar injection of CFA in C57BL/6 mice. JZL195 and WIN55212 both reduced mechanical allodynia and thermal hyperalgesia, and produced catalepsy and sedation in a dose dependent manner. Unlike WIN55212, JZL195 reduced allodynia at doses below those at which side-effects were observed [2].
Mitochondria degrader-1 (example 5) is a potent mitochondria degrader. Mitochondria degrader-1 induces the degradation of the injured mitochondria by the autophagy mechanism. Mitochondria degrader-1 can be used for the research of neurodegenerative disease, cancer, inflammatory disease, age-related disease, metabolic disease, mitochondrial disease or Down's disease[1].
α-Conotoxin Im-I is a selective α7/α9 nAChR antagonist, blocking α7 nicotinic receptors with the highest apparent affinity, while having an 8-fold lower affinity for homomeric α9 nicotinic receptors. α-Conotoxin Im-I is toxic and induces seizures in rodents. α-Conotoxin Im-I is a tool for studying neuronal nAChR[1][2].
Fipexide hydrochloride, a parachloro-phenossiacetic acid derivative, is a nootropic drug. Fipexide hydrochloride reduces striatal adenylate cyclase activity. Fipexide hydrochloride has positive effect on cognitive performance by dopaminergic neurotransmission. Fipexide hydrochloride is used for senile dementia research[1].
Paxilline is an indole alkaloid mycotoxin from Penicillium paxilli, acts as a potent BK channels inhibitor by an almost exclusively closed-channel block mechanism. Paxilline also inhibits the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) with IC50s between 5μM and 50μM for differing isoforms. Paxilline possesses significant anticonvulsant activity[1][2][3].
Miridesap is a ligand for serum amyloid P component (SAP) and intends to inhibit and dissociate SAP binding to amyloid fibrils and tangles.
BoNT-IN-1 is a potent inhibitor of Botulinum neurotoxin A light chain (BoNTA LC) with IC50 of 0.9 uM.IC50 value: 0.9 uMTarget: BoNT in vitro: BoNT-IN-1 targets BoNT/A LC enzymatic activity,is highly efficient in vitro, BoNT-IN-1 has good property in cell-based, as well as tissue-based assays.
Ceralifimod is selective, high potent agonist for sphingosine 1-phosphate receptors 1 and 5, with EC50s of 27.3, 334 pM for human S1P receptor 1 and 5, respectively.
L-Tyrosine-13C9 is the 13C-labeled L-Tyrosine. L-Tyrosine is a non-essential amino acid which can inhibit citrate synthase activity in the posterior cortex.
Tirilazad mesylate (U 74006F) is a nonglucocorticoid, 21-aminosteroid that inhibits lipid peroxidation. Tirilazad mesylate can attenuate brain or spinal cord injury caused by trauma, stroke, ischemia and reperfusion injury. Tirilazad mesylate has antiviral activities against nCoV. Tirilazad mesylate is neuroprotective for ischaemic stroke, can be used for subarachnoid hemorrhage research[1][2][3].
β-Amino Acid Imagabalin Hydrochloride (PD-0332334) is a ligand for the α2δ subunit of the voltage-dependent calcium channel.
Palmitic acid-d4 is the deuterium labeled Palmitic acid. Palmitic acid is a long-chain saturated fatty acid commonly found in both animals and plants. Palmitic acid can induce the expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in in mouse granulosa cells[1][2].
nAChR-IN-1 (hydrochloride) is a tetramethylpiperidine heptanoate, a selective nicotinic acetylcholine receptor (nAChR) inhibitor that inhibits nAChRs lacking α5, α6, or β3 subunits. nAChR-IN-1 has the effect of preventing nerve disorder, can be used for nicotinic acetylcholine receptor dysfunction or neurological disorders research[1].
Eticlopride hydrochloride, a selective dopamine D2‐like receptor antagonist, exhibits high affinity for dopamine D2, α1‐adrenergic, α2‐adrenergic, 5HT1, 5HT2 receptors with Kis of 0.09, 112, 699, 6220, and 830 nM, respectively. Antipsychotic agent[1].
AR-M1896 is a GalR2 selective agonist with a binding IC50 of 1.76 nM for rat GalR2. AR-M1896 can be used for the research of acute myocardial infarction and neuropathic pain[1][2].
Nomifensine maleate is a selective inhibitor of dopamine uptake, used in adult attention deficit disorder.
Rimcazole (BW 234U) is a potent antipsychotic agent. Rimcazole also is a competitive antagonist of sigma sites. Rimcazole can be used for the research of acute schizophrenic diseases[1].
VU0364289 is a highly selective mGlu5 positive allosteric modulator (PAM) (binds to the MPEP (HY-14609A) site), with an EC50 of 1.6 µM. VU0364289 can reverse amphetamine-induced hyperlocomotion in a dose-dependent manner, which can be used for schizophrenia and other psychiatric research[1][2][3].
Ziprasidone Hcl(CP-88059 Hcl) is a combined 5-HT (serotonin) and dopamine receptor antagonist which exhibits potent effects of antipsychotic activity.Target: 5-HT receptor; Dopamine receptorZiprasidone (hydrochloride) is the salt form of ziprasidone, which possesses an in vitro 5-HT2A/dopamine D2 receptor affinity ratio higher than any clinically available antipsychotic agent. In vivo, ziprasidone antagonizes 5-HT2A receptor-induced head twitch with 6-fold higher potency than for blockade of d-amphetamine-induced hyperactivity, a measure of central dopamine D2 receptor antagonism. Ziprasidone also has high affinity for the 5-HT1A, 5-HT1D and 5-HT2C receptor subtypes, which may further enhance its therapeutic potential [1]. Ziprasidone sulfoxide and sulfone were the major metabolites in human serum. The affinities of the sulfoxide and sulfone metabolites for 5-HT2 and D2 receptors are low with respect to ziprasidone, and are thus unlikely to contribute to its antipsychotic effects [2]. Ziprasidone was associated with significant differential adverse effects relative to placebo in BPM, BPD, and schizophrenia with no significant difference in weight gain in all 3 groups. Self-reported somnolence was increased across the 3 conditions. Subjects with BPM were more vulnerable to EPS than those with BPD or schizophrenia [3].Clinical indications: Bipolar I disorder; Bipolar disorder; Mania; SchizophreniaFDA Approved Date: February 2001
N20C hydrochloride is a selective and noncompetitive open NMDA receptor open channel blocker, with micromolar affinity, fast on-off blockade kinetics, and strong voltage dependence. Neuroprotective activity[1].
NMDAR/TRPM4-IN-2 free base (compound 8) is a potent NMDAR/TRPM4 interaction interface inhibitor. NMDAR/TRPM4-IN-2 free base shows neuroprotective activity. NMDAR/TRPM4-IN-2 free base prevents NMDA-induced cell death and mitochondrial dysfunction in hippocampal neurons, with an IC50 of 2.1 μM. NMDAR/TRPM4-IN-2 free base protects mice from MCAO-induced brain damage and NMDA-induced retinal ganglion cell loss[1].
JNJ-63533054 is a potent and selective agonist of hGPR139 with an EC50 = 16 nM.IC50 value: 16 nM (EC50)Target: hGPR139in vitro: JNJ-63533054 is a selective small-molecule agonist. JNJ-63533054 specifically activates human GPR139 in the calcium mobilization (EC50 = 16 ± 6 nM) and GTPγS binding (EC50 = 17 ± 4 nM) assays. [2] JNJ-63533054 is found to be clean of any cross reactivity as judged by an external selectivity panel of 50 known GPCRs, ion channels, and transporters as well as our own internal whole cell lead generation biology selectivity panel.[1]in vivo: JNJ-63533054 is found to cross the blood-brain barrier and have good drug-like properties amenable for oral dosing in rat. JNJ-63533054 exhibits good stability in both human and rat microsomes and high solubility in aqueous media, and no DDI potential was found. [1] JNJ-63533054 also activates the rat and mouse GPR139 receptor with similar potency (rat EC50 = 63 ± 24 nM, mouse EC50 = 28 ± 7 nM). [2]