(R)-Olacaftor ((R)-VX-440) is a Cystic fibrosis transmembrane conductance regulator (CFTR) modulator. (R)-Olacaftor has good potential for the study of cystic fibrosis (CF)[1].
Cenobamate, a sodium channel blocker, enhances GABAergic transmission and has the potential to be a versatile CNS drug.
Remimazolam benzenesulfonate is a GABA agonist。Target: GABA ReceptorRemimazolam acts on GABA receptor, specifically GABA-alpha. Remimazolam is a new drug innovation in anesthesia. Remimazolam combines the properties of two unique drugs already established in anesthesia - Midazolam and remifentanil. Remimazolam acts on GABA receptors like midazolam and has organ-independent metabolism like remifentanil. Remimazolam is likely to be the sedative of the future, as preliminary phase II trials have shown minimal residual effects on prolonged infusions. Remimazolam has potential to be used as a sedative in ICU and as a novel agent for procedural sedation.
Flupirtine Maleate(D 9998) is a selective neuronal potassium channel opener that also has NMDA receptor antagonist properties.IC50 Value: Target: Potassium channel; NMDA receptorin vitro: High concentrations of flupirtine antagonized inward currents to NMDA(200 microM) at -70 mV with an lC50 against steady-state responses of 182.1+/-12.1 microM. The effects of flupirtine were voltage-independent and not associated with receptor desensitization making actions within the NMDA receptor channel or at the glycine modulatory site unlikely. NMDA receptor antagonism probably has little relevance for the clinical efficacy of flupirtine as the concentrations needed were far higher than those achieved in clinical practice. However, the activation of a G-protein-regulated inwardly rectifying K+ channel was identified as an interesting molecular target site of flupirtine. In the next stage, the central nervous spectrum of action of experimental K+ channel openers (PCO) was considered. As far as they have been studied, experimental K+ channel openers display a spectrum of action comparable to that of flupirtine [1]. Therapeutic flupirtine concentrations (≤10 μM) did not affect voltage-gated Na(+) or Ca(2+) channels, inward rectifier K(+) channels, nicotinic acetylcholine receptors, glycine or ionotropic glutamate receptors. Flupirtine shifted the gating of K(V)7 K(+) channels to more negative potentials and the gating of GABA(A) receptors to lower GABA concentrations [2]. Cell exposure to flupirtine decreased the amplitude of delayed rectifier K(+) current (I(K(DR))) with a concomitant raise in current inactivation in NSC-34 neuronal cells [4].in vivo: Rats were trained to discriminate the novel analgesic flupirtine (10.0 mg/kg i.p., 10 min) from no drug under a two-choice fixed-ratio 5 shock-termination schedule. Flupirtine yielded a dose-response curve with an ED50 of 3.87 mg/kg. The opioid analgesics pentazocine, codeine and tramadol failed to produce flupirtine appropriate responding. The opioid antagonist naltrexone did not antagonize the discriminative effects of flupirtine [3]. Both morphine (ED50=0.74 mg/kg) and flupirtine (ED50=3.32 mg/kg) caused dose-related anti-hyperalgesia at doses that did not cause sedation [5]. Toxicity: Based on study-end data, hepatotoxicity was detected in 31% of patients receiving flupirtine for ≥ 6 weeks [6].
Linalool is natural monoterpene in essential olis of coriander, acts as a competitive antagonist of Nmethyl d-aspartate (NMDA) receptor, with anti-tumor, anti-cardiotoxicity activity[1].
3-Chlorodiphenylamine is a high affinity Ca2+ sensitizer of cardiac muscle. 3-Chlorodiphenylamine is based on diphenylamine and binds to the isolated N-domain of cardiac troponin C (cTnC) (Kd=6 µM). 3-Chlorodiphenylamine is an excellent starting scaffold for the development of more potent Ca2+-sensitizing compounds due to its small size, and can be used for systolic heart failure research[1].
AE0047 Hydrochloride is a calcium blocker, used in the research of hypertensive disease.
Riluzole is an anticonvulsant drug and belongs to the family of use-dependent Na+ channel blocker which can also inhibit GABA uptake with an IC50 of 43 μM.
Ethyl tosylcarbamate is an intermediate in the synthesis of Gliclazide (G409877)[1][2]. Gliclazide is a whole-cell beta-cell ATP-sensitive potassium currents blocker with an IC50 of 184 nM[3].
Dofetilide D4 (UK 68789 D4) is a deuterium labeled Dofetilide. Dofetilide is a class III antiarrhythmic agent.
Levemopamil hydrochloride is a blood-brain barrier penetrable calcium channel blocker and a 5-HT2 antagonist. Levemopamil hydrochloride can be used for temporary occlusion and neurological disease research[1].
KCNQ1 activator-1 (compound 3) is a potent activator of KCNQ1 channel. KCNQ1 activator-1 has the potential for the research of long QT syndrome (LQTS)[1].
cis-ACPD is a potent agonist of NMDA receptor, with an IC50 of 3.3 μM. And it is also a selective agonist of group II mGluR, with EC50s of 13 μM and 50 μM for mGluR2 and mGluR4, respectively[1][2].
Thiocolchicoside is a competitive γ-aminobutyric acid type A (GABAA) receptor antagonist and glycine receptor agonist in the central nervous system. Thiocolchicoside is a semisynthetic sulfur derivative of colchicoside. Thiocolchicoside is a muscle relaxant and has anti-inflammatory, and analgesic properties[1].
Pilsicainide (SUN 1165 free acid) is a potent sodium channel blocker and potent class Ic antiarrhythmic agent[1][2].
(±)-HIP-A is a non-competitive excitatory amino acid transporter (EAAT) blocker that effectively blocks Glu uptake (IC50=17-18 μM). (±)-HIP-A is also a lead compound against ischemia-induced neuronal degeneration. (±)-HIP-A can be used in the study of neurological diseases[1].
9-Phenanthrol (9-Hydroxyphenanthrene) is a potent and selective human TRPM4 inhibitor, with an IC50 of 20 μM. 9-Phenanthrol can be used for the research of ischemia-reperfusion injury[1][2].
Quinidine hydrochloride monohydrate is a clinical anti-arrythmic drug which is also a potent blocker of K+ channel with an IC50 of 19.9 μM.
Tannic acid is a novel hERG channel blocker with IC50 of 3.4 μM.
(+)-SJ733 is a clinical candidate for malaria which can also inhibit Na+-ATPase PfATP4.
Felbamate-d4 (W-554-d4) is the deuterium labeled Felbamate. Felbamate (W-554) is a potent nonsedative anticonvulsant whose clinical effect may be related to the inhibition of N-methyl-D-aspartate (NMDA).
Cl-HIBO is a highly subtype-selective GluR1/2 agonist (EC50=4.7 and 1.7 μM, respectively). Cl-HIBO is a potent AMPA receptor agonist (IC50=0.22 μM). Cl-HIBO has desensitizing properties[1].
Lansoprazole sodium(AG-1749) is a proton pump inhibitor which prevents the stomach from producing acid.Target: Proton PumpLansoprazole (sodium) is sodium salt form of lansoprazole, lansoprazole, a substituted benzimidizole proton pump inhibitor, on pharmacokinetics and metabolism of theophylline has been studied in healthy adults given oral lansoprazole 30 mg once daily for 11 days. On Days 4 and 11 of 300 mg aminophylline was simultaneously administered orally and blood samples for theophylline analysis were taken over 24 h [1]. Patients in the lansoprazole group were significantly less likely to have a recurrence of ulcer complications than patients in the placebo group (P=0.008). There was no significant difference in mortality between the two groups [2]. lansoprazole (AG-1749) and omeprazole, were found to have significant activities against this organism. The activity of lansoprazole was comparable to that of bismuth citrate, with MICs ranging from 3.13 to 12.5 micrograms/ml, and fourfold more potent than that of omeprazole [3]. Clinical indications: Duodenal ulcer; Esophagitis; Gastroesophageal reflux; Gastrointestinal disease; Helicobacter pylori infection; Peptic ulcer; Stomach ulcer; Ulcer; Zollinger-Ellison syndromeFDA Approved Date: May 10, 1995Toxicity: Symptoms of overdose include abdominal pain, nausea and diarrhea.
Sematilide hydrochloride (CK-1752 hydrochloride) is a selective IKr channel blocker. Sematilide causes a concentration-dependent inhibition of the delayed rectifier K+ current (IC50=25 μM). Sematilide is a class III antiarrhythmic agent[1].
Omeprazole sodium (H 16868 sodium), a proton pump inhibitor (PPI), is available for treatment of acid-related gastrointestinal disorders. Omeprazole sodium shows competitive inhibition of CYP2C19 activity with a Ki of 2 to 6 μM[1]. Omeprazole sodium also inhibits growth of Gram-positive and Gram-negative bacteria[2]. Omeprazole is a potent brain penetrant neutral sphingomyelinase (N-SMase) inhibitor (exosome inhibitor)[3].
Ivacaftor hydrate is an orally bioavailable CFTR potentiator, used for cystic fibrosis treatment.
(Rac)-AZD3839 is an orally active beta-amyloid precursor protein cleaving enzyme (BACE1) inhibitor that is blood-brain barrier-permeable. (Rac)-AZD3839 has an affinity for the human ether-a-go-go related gene (hERG) ion channel. (Rac)-AZD3839 can be used in the research of Alzheimer's disease[1].
4-(Phenyldiazenyl)benzoic acid is a photosensitive and photoswitchable TRPA1 agonist that can be used as pharmacological tools for study of pain signaling.
Fluoroethylnormemantine, a derivative of Memantine, is an antagonist of the N-methyl-D-aspartate (NMDA) receptor. [18F]-Fluoroethylnormemantine can be used as a positron emission tomography (PET) tracer. Fluoroethylnormemantine exhibits anti-amnesic, neuroprotective, antidepressant-like and fear-attenuating effects[1][2][3].
(±)-HIP-B is a non-competitive excitatory amino acid transporter (EAAT) blocker that effectively blocks Glu uptake (IC50=17-18 μM). (±)-HIP-B is also a lead compound against ischemia-induced neuronal degeneration. (±)-HIP-B can be used in the study of neurological diseases[1].