Flupirtine(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 ?M) 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 (ED?? =?0.74?mg/kg) and flupirtine (ED???=?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].
Mepivacaine is a tertiary amine used as a local anesthetic.Target: Sodium ChannelMepivacaine is a local anesthetic of the amide type. Mepivacaine has a reasonably rapid onset (more rapid than that of procaine) and medium duration of action (shorter than that of procaine). Mepivacaine is used in any infiltration and regional anesthesia. It is supplied as the hydrochloride salt of the racemate [1]. Mepivacaine displayed a preferential use-dependent block of Na(v)1.8, S(-)-bupivacaine displayed a preference for TTXs Na(+) channels [2].
Urocortin, rat is a selective agonist of CRF receptor, with Kis of 0.32, 2.2, and 0.62 nM for hCRF1, rCRF2α and mCRF2β, respectively.
Luzindole (N-0774) is a selective melatonin receptor antagonist. Luzindole preferentially targets MT2 (Mel1b) over MT1 (Mel1a) with Ki values of 10.2 and 158 nM for human MT2 and MT1, respectively. Luzindole suppresses experimental autoimmune encephalomyelitis (EAE), and exerts antidepressant-like activity[1][2][3].
Escitalopram is a selective serotonin reuptake inhibitor (SSRI) with Ki of 0.89 nM.Target: SSRIsEscitalopram, the S-enantiomer of citalopram, belongs to a class of antidepressant agents known as selective serotonin-reuptake inhibitors (SSRIs). Escitalopram may be used to treat major depressive disorder (MDD) and generalized anxiety disorder (GAD). Escitalopram has no significant affinity for adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors; antagonism of such receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs. The chronic administration of escitalopram is found to downregulate brain norepinephrine receptors, as has been observed with other drugs effective in the treatment of major depressive disorder. Escitalopram does not inhibit monoamine oxidase.
Dihexa is an orally active, blood-brain barrier-permeable angiotensin IV analog; exhibits high affinity binding hepatocyte growth factor (HGF) with a Kd of 65 pM.
Chlormezanone resembles benzodiazepine. The action of Chlormezanone is similar to benzodiazepine-type agents. Chlormezanone is used as an anxiolytic and a muscle relaxant.
(-)-(S)-B-973B is a potent allosteric agonism and positive allosteric modulation (ago-PAM) for α7 nAChR, with antinociceptive activity[1].
NS1738 is a novel positive allosteric modulator of the α7 nAChR, with respect to positive modulation of α7 nAChR (EC50=3.4 μM in oocyte experiments).
MAO-IN-1 is a monoamine oxidase B (MAO B) inhibitor with an IC50 of 20 nM.
Dapoxetine-d6 is the deuterium labeled Dapoxetine[1]. Dapoxetine (LY-210448) is an orally active and selective serotonin reuptake inhibitor (SSRI). Dapoxetine can be used for the research of premature ejaculation (PE)[2].
Paliperidone (9-hydroxyrisperidone) is a dopamine antagonist of the atypical antipsychotic class of medications. IC50 value:Target: dopamine receptorin vitro: Paliperidone inhibited MK-801 induced neurotoxicity both in MTT metabolism assay (p<0.01) and in lactate dehydrogenase (LDH) activity assay (p<0.01). Moreover, paliperidone could significantly retard MK-801-mediated inhibition of neurite outgrowth (p<0.01) and reverse MK-801-induced decreases of gene expression and phosphorylation of Akt1 and GSK3β (both p<0.01). Furthermore, these protective effects of paliperidone were blocked by pretreatment with a PI3K inhibitor LY294002 [1]. paliperidone works finely at low concentrations (10 and 50 μM) against Aβ(25-35) and MPP(+) and solely protected SH-SY5Y from hydrogen peroxide. At 100 μM, paliperidone completely diminished cell reduction induced by different stressors, regardless of their dosages. Paliperidone was demonstrated with a higher oxidative stress-scavenging properties than other APDs in several aspects, such as generated bulk glutathione, low HNE, and protein carbonyl productions [2].in vivo: The 9OHRIS (4 mg/bwkg) was administred by gastric tube. Four groups were formed depending on the treatment: (1) control, (2) stress, (3) 9OHRIS, (4) stress and parallel 9OHRIS treatment (n=5-6). The expression of APP, MAPK1, β-actin mRNAs from the perfused brain samples was measured with real-time PCR technique [3].Male offspring were treated orally via drinking water with vehicle, risperidone (0.01mg/kg/day), or paliperidone (0.01mg/kg/day) between postnatal days 35 and 56 (periadolescence) and extracellular glutamate levels in the prefrontal cortex were determined by microdialysis at PD 56 [4].
L-Hisidine is an essential amino acid for infants. L-Hisidine is an inhibitor of mitochondrial glutamine transport.
Lp-PLA2-IN-4 is a potent inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2). Lp-PLA2 previously known as platelet- activating factor acetylhydrolase (PAF-AH), is a phospholipase A2 enzyme involved in hydrolysis of lipoprotein lipids or phospholipids. Lp-PLA2-IN-4 has the potential for the research of diseases associated with the activity of Lp-PLA2, for example atherosclerosis, Alzheimer's disease (extracted from patent WO2021228159A1, compound 38)[1].
Pridinol mesylate is an orally active and potent central anticholinergic agent, and acts as muscle relaxant[1].
Phyllomedusin, an tachykinin decapeptide, is a NK1 receptor agonist. Phyllomedusin has vasodilating activity and provokes the contraction of the pylorus[1][2][3].
Pergolide Mesylate is an antiparkinsonian agent which functions as a dopaminergic agonist.Target: Dopamine ReceptorPergolide mesylate (trade name Permax) is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinson's disease. Pergolide mesylate functions as an agonist at the dopamine D2, D1 and serotonin 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, and 5-HT2C receptors. It may possess agonist activity at other dopamine receptor subtypes as well, similar to cabergoline [1, 2]. Pergolide mesylate decreases plasma prolactin concentrations [3]. The weak agonist activity of pergolide at D1 receptors somewhat alters its clinical and side effect profile in the treatment of Parkinson's disease. The drug is in decreasing use, as it is reported to be associated with a form of heart disease called cardiac fibrosis. The use of pergolide or cabergoline is associated with a significantly increased risk of newly diagnosed cardiac-valve regurgitation [4].
Pipenzolate bromide is a muscarinic receptor antagonist, preventing acetyl choline from binding to the receptors.
AEG3482 is a potent antiapoptotic compound that inhibits Jun kinase (JNK) activity through induced expression of heat shock protein 70 (HSP70). AEG3482 directly binds HSP90, thereby facilitating HSF1-dependent expression of HSP70 and HSP25[1].
α-Synuclein (71-82) (human) is the 71-82 fragment of α-Synuclein. α-Synuclein is an abundant neuronal protein that is highly abundant in presynaptic nerve terminals. α-Synuclein is a biomarker for Parkinson's disease (PD)[1].
Rivastigmine tartrate, an cholinesterase inhibitor(IC50= 5.5 uM), inhibits both butyrylcholinesterase and acetylcholinesteraseIC50 value: 5.5 uMTarget: AChERivastigmine is a parasympathomimetic or cholinergic agent for the treatment of mild to moderate dementia of the Alzheimer's type and dementia due to Parkinson's disease. The drug can be administered orally or via a transdermal patch; the latter form reduces the prevalence of side effects, which typically include nausea and vomiting. The drug is eliminated through the urine, and appears to have relatively few drug-drug interactions. Rivastigmine, a cholinesterase inhibitor, inhibits both butyrylcholinesterase and acetylcholinesterase. It is thought to work by inhibiting these cholinesterase enzymes, which would otherwise break down the brain chemical acetylcholine.
Dehydromaackiain is a potent Neurogenin2 (Ngn2) promoter activator. Dehydromaackiain promotes differentiation of neural stem cells into neurons[1].
SC-51089 is a selective antagonist of EP1 receptor with analgesic activity in vivo[1].
PW0787 is a potent, selective, orally active, and brain-penetrant GPR52 agonist (EC50=135 nM). PW0787 suppresses psychostimulant behavior[1].
Gamma-Glu-Abu is a potent calcium sensing receptor (CaSR) agonist[1].
VU6000918 is a muscarinic acetylcholine (M4) positive allosteric modulator, with an EC50 of 19 nM for hM4[1].
Panamesine (EMD 57445) is a sigma receptor ligand, which has a high affinity (IC50 6 nM) and selectivity for sigma binding sites. Panamesine is a potential atypical neuroleptic agent[1].
RP-001 hydrochloride is a picomolar short-acting S1P1 (EDG1) selective agonist, with an EC50 of 9 pM. RP-00 hydrochloride induces internalization and polyubiquitination of S1P1. RP-001 hydrochloride has little activity on S1P2-S1P4 and only moderate affinity for S1P5[1].
Oxyfenamate has anti-anxiety actions for use in anxiety neuroses.
Mosapride citrate is a gastroprokinetic agent that acts as a selective 5HT4 agonist.Target: 5HT4 Mosapride is a gastroprokinetic agent that acts as a selective 5HT4 agonist. The major active metabolite of mosapride, known as M1, additionally acts as a 5HT3 antagonist, which accelerates gastric emptying throughout the whole of the gastrointestinal tract in humans, and is used for the treatment of gastritis, gastro-oesophageal reflux disease, functional dyspepsia and irritable bowel syndrome. It is recommended to be taken on an empty stomach (i.e. at least one hour before food or two hours after food).In addition to its prokinetic properties, mosapride also exerts anti-inflammatory effects on the gastrointestinal tract which may contribute to some of its therapeutic effects. Mosapride also promotes neurogenesis in the gastrointestinal tract which may prove useful in certain bowel disorders. The neurogenesis is due to mosapride's effect on the 5-HT4 receptor where it acts as an agonist.Its common side effects include dry mouth, abdominal pain, dizziness, headache, insomnia, malaise, nausea, diarrhoea and sometimes constipation. Unlike some other prokinetic agents, mosapride has little effect on potassium channels, no effect on hERG transfected cells, and no effect on cardiovascular function that could be detected in tests on humans. Due to the pharmacokinetics of mosapride, it would take 1,000 - 3,000 times the therapeutic dose to elicit cardiovascular effects.