trans-ACBD (trans-1-Aminocyclobutane-1,3-dicarboxylic acid) is a very potent and selective NMDA receptor agonist that modulates glutamatergic neurotransmission[1].
Sumatriptan succinate (GR 43175) is a serotonin1 (5-HT1) receptor agonist, which is effective in the acute treatment of migraine headache.Target: 5-HT 1d receptor agonistSumatriptan succinate is a serotonin1 (5-HT1) receptor agonist, which is effective in the acute treatment of migraine headache. Its antimigraine activity is believed to derive from selective vasoconstriction of cranial blood vessels which are dilated and distended during migraine headache and/or from inhibition of neurogenically mediated inflammation in the dura mater [1].For sumatriptan succinate 50 mg versus placebo the NNTs were 6.1, 7.5, and 4.0 for pain-free at two hours and headache relief at one and two hours, respectively. NNTs for sustained pain-free and sustained headache relief during the 24 hours postdose were 9.5 and 6.0, respectively [2]. Difference in time-weighted (0-2.5 h) mean arterial pressure MAP (90% confidence interval) was 1.2 mmHg (-0.2, 2.7) between telcagepant and placebo, 4.0 mmHg (2.5, 5.5) between sumatriptan succinate and placebo, and 1.5 mmHg (0.0, 3.0) between telcagepant with sumatriptan succinate vs sumatriptan succinate alone. When coadministered with telcagepant, the AUC0-6h and C(max) of sumatriptan succinate were increased by 23% and 24%, respectively. The small MAP increases observed after coadministration could possibly be associated with the slight elevations in sumatriptan succinate levels [3].Clinical indications: Cluster headache; MigraineToxicity: Symptoms of overdose include convulsions, tremor, paralysis, inactivity, ptosis, erythema of the extremities, abnormal respiration, cyanosis, ataxia, mydriasis, salivation, and lacrimation
Glycerophosphoinositol choline is an essential nutrient that activates alpha7 nicotinic receptors and has analgesic and anti-inflammatory activity. Glycerophosphoinositol choline can affect diseases such as liver disease, atherosclerosis and neurological disorders[1][2].
Cisapride monohydrate is an orally and potent 5-HT4 receptor agonist and hERG inhibitor. Cisapride monohydrate is an prokinetic agent which facilitates or restores motility throughout the length of the gastrointestinal tract. Cisapride monohydrate stimulates gastrointestinal motor activity through an indirect mechanism involving the release of acetylcholine mediated by postganglionic nerve endings in the myenteric plexus of the gut[1][2].
(E)-3,4,5-Trimethoxycinnamic acid (TMCA) is a cinnamic acid substituted by multi-methoxy groups. (E)-3,4,5-Trimethoxycinnamic acid is an orally active and potent GABAA/BZ receptor agonist. (E)-3,4,5-Trimethoxycinnamic exhibits favourable binding affinity to 5-HT2C and 5-HT1A receptor, with IC50 values of 2.5 and 7.6 μM, respectively. (E)-3,4,5-Trimethoxycinnamic acid shows anticonvulsant and sedative activity. (E)-3,4,5-Trimethoxycinnamic acid can be used for the research of insomnia, headache and epilepsy[1][2][3].
Calcitonin human is an endogenous calcitonin receptor agonist.Calcitonin human lowers systemic blood calcium levels and inhibits bone resorption.
AChE/GSK-3β-IN-1 (compound GT15) is a potent, dual AChE/GSK-3β inhibitor with IC50 values of 1.2, 149.8 and 22.4 nM for hAChE , hBChE and hGSK-3β, respectively. AChE/GSK-3β-IN-1 penetrates the blood-brain barrier (BBB). AChE/GSK-3β-IN-1 has high kinase selectivity profiles for the CMGC kinase family. AChE/GSK-3β-IN-1 occupies the ATP binding site of DYRK1A. AChE/GSK-3β-IN-1 inhibits ROS expression and reduces oxidative stress. AChE/GSK-3β-IN-1 can be used for Alzheimer’s disease research[1].
Brexpiprazole S-oxide (DM-3411) is a main metabolite of Brexpiprazole and is metabolized by cytochrome P450 3A4 (CYP3A4). Brexpiprazole is an atypical antipsychotic agent and a partial agonist of human 5-HT1A and dopamine receptor with Kis of 0.12 nM and 0.3 nM, respectively. Brexpiprazole is also a 5-HT2A receptor antagonist with a Ki of 0.47 nM[1][2][3].
Arborine, isolated from Glycosmis arborea, inhibits the peripheral action of acetylcholine and induces a fall in blood pressure[1][1].
Tenuifolin is a triterpene isolated from Polygala tenuifolia Willd, has neuroprotective effects. Tenuifolin reduces Aβ secretion by inhibiting β-secretase. Tenuifolin improves learning and memory in aged mice by decreasing AChE activity and has the potential for Alzheimer’s disease (AD) treatment[1].
A potent and selective α4β2 nAChR agonist with Ki of 16 nM; display selectivity over α7 nAChR (Ki>10 uM) and α1β1 nAChR; displays a similar potency and efficacy to (-)-nicotine to facilitate ACh release (EC50=3 uM), with less potent and less efficacious stimulate dopamine release (ABT-089, EC50=1.1 uM; (-)-nicotine, EC50=0.04 uM); shows effects on cognitive performance in rats and monkeys. Alzheimer Disease Phase 2 Discontinued
Tropisetron(SDZ-ICS 930) is a selective 5-HT3 receptor antagonist and α7-nicotinic receptor agonist with an IC50 of 70.1 ± 0.9 nM for 5-HT3 receptor. IC50 value: 70.1 ± 0.9 nM [1]Target: 5-HT3 receptorin vitro: Tropisetron specifically inhibited both IL-2 gene transcription and IL-2 synthesis in stimulated T cells. tropisetron inhibited both the binding to DNA and the transcriptional activity of NFAT and AP-1. We also observed that tropisetron is a potent inhibitor of PMA plus ionomycin-induced NF-(kappa)B activation but in contrast TNF(alpha)-mediated NF-(kappa)B activation was not affected by this antagonist [2]. Tropisetron prevents the phosphorylation and thus activation of the p38 MAPK, which is involved in post-transcriptional regulation of various cytokines [3].in vivo: Two different doses of tropisetron (5 and 10 mg/kg) or vehicle were administered intraperitoneally 30 min before pMCAO. Neurological deficit scores, mortality rate and infarct volume were determined 24 h after permanent focal cerebral ischemia [4].
TC-F2 is a reversible non-covalent binding inhibitor of fatty acid amide hydrolase (FAAH) with an IC50 of 28 nM. FAAH is involved in many human diseases, particularly cancer, pain and inflammation as well as neurological, metabolic and cardiovascular disorders[1].
Alpha-Asarone is one of the main psychoactive compounds, and possesses an antidepressant-like activity in mice.IC50 value:Target:In vitro: The results indicated that α-asarone significantly attenuated the LPS-stimulated increase in neuroinflammatory responses and suppressed pro-inflammatory cytokine production in BV-2 cells. Mechanistic study revealed that α-asarone?inhibited the LPS-stimulated activation via regulation of nuclear factor kappa-B by blocking degradation of inhibitor kappa B-alpha signaling in BV-2 microglial cells. [2]In vivo: The present results reveal that the acute treatment of α-asarone elicited biphasic responses on immobility such that the duration of the immobility time is significantly reduced at lower doses (15 and 20 mg/kg, i.p.) but increased at higher doses (50 and 100 mg/kg, i.p.) in the TST. Besides, α-asarone at higher doses (50 and 100 mg/kg, i.p.) significantly decreased the spontaneous locomotor activity.[1]
Pilocarpine nitrate is a selective M3-type muscarinic acetylcholine receptor (M3 muscarinic receptor) agonist.
(N-Me-Tyr1,N-Me-Arg7,D-Leu-NHEt8)-Dynorphin A (1-8) (E-2078), a stable Dynorphin A (1–8) (HY-P2159) analog, is a kappa opioid receptor (KOR) agonist[1].
Piribedil hydrochloride is a potent and orally active dopamine D2 and dopamine D3 agonist. Piribedil hydrochloride is also a α2-adrenoceptors antagonist. Piribedil hydrochloride can inhibit MLL1 methyltransferase activity (EC50: 0.18 μM). Piribedil hydrochloride has the potential for the research of parkinson's disease, circulatory disorders, cancers[1][2][3][4].
Methapyrilene is a histamine antagonist, a pyridine chemical with anticholinergic activity. Methapyrilene can cause target organ-specific epigenetic alterations, such as a decrease in DNA methylation levels. Methapyrilene induces hepatocellular carcinoma in rats[1][2].
Trap-101 hydrochloride is a potent, selective and competitive antagonist of NOP receptors over classical opioid receptors. Trap-101 stimulates GTPγ35S binding to CHOhNOP membranes with pKi values of 8.65, 6.60, 6.14 and <5 for NOP, μ-, κ-, and δ-opioid receptors, respectively. Trap-101 attenuates motor deficits in a rat model of parkinson's disease and can be used for the research of nervous system diseases[1].
GR 159897 is a highly potent, selective, competitive, brain-penetrated non-peptide antagonist at tachykinin NK2 receptors, inhibits binding of [3H]GR100679 to hNK2-CHO cells and rat colon membranes with pKis of 9.51 and 10, respectively. Antagonizes bronchoconstriction, with anxiolytic-like activity[1].
Telenzepine is an antimuscarinic agent with Kis of 0.94 nM (M1 mAChR) and 17.8 nM (M2 mAChR) binding to muscarinic receptors. Telenzepine effectively blocks synaptic transmission promoted by muscarinic or M1 receptor agonists. Thus, Telenzepine can reduce the amplitude of extracellular slow excitatory postsynaptic potentials (EC50=38 nM) and slow inhibitory postsynaptic potentials (EC50=253 nM)[1].
EMDT oxalate is a selective 5-HT6 agonist, and has antidepressant effects[1].
FPPQ is a dual-acting 5-HT3 (Ki = 0.9 nM) and 5-HT6 (Ki = 3 nM) receptor antagonist with antipsychotic and procognitive properties.
Atabecestat (JNJ-54861911, JNJ54861911) is a novel potent, oral beta-secretase (BACE) inhibitor for treatment of Alzheimer's Disease.
Tasimelteon is a melatonin MT1 and MT2 receptor agonist.Target: melatonin receptorTasimelteon is a novel circadian regulator, is the first product for the treatment of Non-24-hour Sleep-Wake Disorder (Non-24) approved by either the FDA or the European Medicines Agency (EMA). Tasimelteon is a potent and specific melatonin (MT1 and MT2) receptor agonist with 2 - 4 times greater affinity for the MT2 receptor.
Bodipy TMR-X muscimol is a Bodipy labeled Muscimol (HY-N2313) (Ex=543 nm, Em=572 nm). Muscimol is a GABAA agonist. Bodipy TMR-X muscimol can be used for imaging the spread of reversible brain inactivations[1].
Syk Inhibitor II is a potent, high selective and ATP-competitive Syk inhibitor with an IC50 of 41 nM. Syk Inhibitor II inhibits 5-HT release from RBL-cells with an IC50 of 460 nM. Syk Inhibitor II shows less potent against other kinases and has anti-allergic effect[1].
LY 392098 is a selective, potent and centrally active positive allosteric modulator of AMPAR; enhances glutamate (100 uM) stimulated ion influx through recombinant homomeric human AMPAR ion channels with EC50 of 1.77 uM (GluR1(i)), 0.22 uM (GluR2(i)), 0.56 uM (GluR2(o)), 1.89 uM (GluR3(i)) and 0.20 uM (GluR4(i); enhances a dose-dependent manner responses to AMPA, potentiates the synaptic excitation of dentate granule cells following perforant path stimulation in vivo.
Viminol is a centrally acting analgesic agent. Viminol also shows antitussive activity[1][2].
BAM-22P, a highly potent opioid peptide, is a potent opioid agonist.