Tiagabine(NO328) is a selective gamma-aminobutyric acid (GABA) reuptake inhibitor.Target: GABA reuptake inhibitorTiagabine had an early onset of effect, as shown by significant reduction from baseline in mean HAM-A total score compared with placebo at week 1 (observed cases, p < .05). Tiagabine was generally well tolerated and not associated with changes in sexual functioning or depressive status. Symptoms of a discontinuation syndrome during taper were not observed. Tiagabine may be a useful treatment option for adult patients diagnosed with GAD [1]. Tiagabine was generally well tolerated; the most common adverse events were nausea, dizziness and headaches [2]. Tiagabine (0.1 microM), an antiepileptic drug that specifically inhibits the GAT-1 GABA transporter inhibited GABA uptake 50% in temporal cortex and 60-68% in white structures [3].
QX-314 chloride is a membrane-impermeable permanently charged sodium channel blocker[1].
Istaroxime is a potent inhibitor of Na+,K+-ATPase with IC50 of 0.11 μM.
AP-18, a potent and selective TRPA1 inhibitor, blocks activation of TRPA1 by 50 μM Cinnamaldehyde with an IC50 of 3.1 μM and 4.5 μM for human and mouse TRPA1, respectively. AP-18 reverses complete Freund's adjuvant (CFA)-induced mechanical hyperalgesia in mice. AP-18 attenuated 30 μM AITC-induced Yo-Pro uptake in a concentration-dependent manner, with an IC50 of 10.3 μM[1][2][3].
Caloxin 2A1 is an extracellular plasma membrane Ca2+-ATPase (PMCA) peptide inhibitor. Caloxin 2A1 does not affect basal Mg2+-ATPase or Na+-K+-ATPase[1].
Fluoroethylnormemantine hydrochloride, a derivative of Memantine, is an antagonist of the N-methyl-D-aspartate (NMDA) receptor. [18F]-Fluoroethylnormemantine hydrochloride can be used as a positron emission tomography (PET) tracer. Fluoroethylnormemantine hydrochloride exhibits anti-amnesic, neuroprotective, antidepressant-like and fear-attenuating effects[1][2][3].
Remogliflozin is a potent and selective inhibitor of SGLT2 (sodium-glucose cotransporter 2) with Kis of 12.4 and 26 nM for human and rat SGLT2, respectively[1].
DPO-1 is a potent inhibitor of the voltage-gated potassium channel subtype Kv1.5 and a blocker of ultrarapid delayed rectifier potassium current. DPO-1 prevents atrial arrhythmia[1][2].
A-317567 is a potent acid-sensing ion channel 3 (ASIC-3) inhibitor with an IC50 of 1.025 μM. A-317567 has antidepressant and antinociception effects[1][2].
AZD7325 is a potent and orally active partial selective PAM of GABAAα2 and Aα3 receptor (Ki=0.3 and 1.3 nM, respectively), and has less antagonistic efficacy at the Aα1 and Aα5 receptor subtypes[1][4]. AZD7325 is a moderate CYP1A2 and a potent CYP3A4 inducer in vitro[2]. AZD7325 has the potential for the investigation of anxiety and dravet syndrome[3]. PAM: positive allosteric modulator.
N-type calcium channel blocker-1 is an orally active analgesic agent which shows high affinity to functionally block N-type calcium channels with an IC50 of 0.7 μM in the IMR32 assay.
(RS)-AMPA ((±)-AMPA) is a glutamate analogue and a potent and selective excitatory neurotransmitter L-glutamic acid agonist. (RS)-AMPA does not interfere with binding sites for kainic acid or NMDA receptors[1][2].
SK3 Channel-IN-1 (compound 7a) is a potent and specific SK3 channel modulator. SK3 Channel-IN-1 has efficient effect on breast cancer MDA-MB-435 cell migration while exhibiting low cytotoxicity in other cell lines. SK3 Channel-IN-1 can modulate ion channels’activity in cancer[1].
Ropivacaine HCl is an anaesthetic agent and blocks impulse conduction in nerve fibres through inhibiting sodium ion influx reversibly.Target: Sodium ChannelRopivacaine is a new long-acting local anesthetic, with vasoconstrictive properties. Ropivacaine given epidurally provided adequate sensory anesthesia and motor block for transurethral surgery. Addition of epinephrine did not provide any significant prolongation of the sensory or motor block, nor any influence upon the sympathetic block [1]. Ropivacaine was metabolized to 2',6'-pipecoloxylidide (PPX), 3'-hydroxyropivacaine (3'-OH Rop), and 4'-hydroxyropivacaine (4'-OH Rop) by hepatic microsomes from human and rat. Ropivacaine N-dealkylation and 3'-hydroxylation activities correlated well with the level of CYP3A4 and 1A2 in human hepatic microsomes, respectively [2].
NSC23925 is a novel, selective and effective P-glycoprotein (Pgp) inhibitor.
(RS)-CPP ((±)-CPP) is a potent and selective NMDA antagonist. (RS)-CPP inhibits central neuron responses, and has anticonvulsant activity[1].
A novel potent and selective negative modulator of AMPA receptors containing TARP-gamma8
CP-100356 hydrochloride is an orally active dual MDR1 (P-gp)/BCRP inhibitor, with an IC50s of 0.5 and 1.5 µM for inhibiting MDR1-mediated Calcein-AM transport and BCRP-mediated Prazosin transport, respectively. CP-100356 hydrochloride is also a weak inhibitor of OATP1B1 (IC50=∼66 µM). CP-100356 hydrochloride is devoid of inhibition against MRP2 and major human P450 enzymes (IC50>15 µM)[1].
S-(+)-Mecamylamine (hydrochloride) is a neuronal nicotinic receptor modulator with antidepressant activity.
AMG9678 is a potent, selective, orally active antagonist of TRPM8 with an IC50 of 31.2 nM[1].
GDC-0334 is a TRPA1 antagonist useful in treatment TRPA1-mediated diseases, such as pain or asthma.
gamma-DGG is a competitive AMPA receptor blocker.
WY-47766, a proton pump inhibitor, is used potentially for the treatment of postmenopausal osteoporosis.
TMB-8 is a novel Ca 2+ antagonist. TMB-8 may exert inhibitory effects in smooth muscle by blocking Ca 2+ release from intracellular bound stores.
A2793 is an efficient TWIK-related acid-sensitive K+ channel (TASK)-1 inhibitor, with an IC50 of 6.8 μM[1].
GABAA receptor agent 1 is a high affinity ligand for GABAA receptor, with potent anticonvulsant activity[1].
AZD-1305 is an antiarrhythmic agent and atrial selective sodium channel/potassium channel blocker, which can significantly prolongs action potential duration and reduces excitability, cause atrial selective ERP prolongation and acute termination of atrial fibrillation. AZD1305 can be used for atrial fibrillation research[1][2].
BBT is an enhancer of impaired glucose-stimulated insulin secretion (GSIS). BBT exhibits anti-hyperglycemia activity, and protects β-cells from cytokine- or streptozotocin (STZ)-induced cell death in type 2 diabetes models. BBT acts function via cAMP/PKA and long-lasting (L-type) voltage-dependent Ca2+ channel/CaMK2 pathway[1].
(-)-Borneol has a highly efficacious positive modulating action at GABA receptor with an EC50 of 237 μM.
Propanidid (Sombrevin; Fabantol) is a γ-aminobutyric acid type A (GABAA) receptor agonist and a short-acting non-barbiturate general anesthetic agent. Propanidid can decrease the arterial pressure[1][2].