NFPS is a selective, non-competitive glycine transporter-1 (GlyT1) inhibitor with IC50s of 2.8 nM and 9.8 nM for hGlyT1 and rGlyT1, respectively[1]. NFPS exerts neuroprotection via glyR alpha1 subunit in the rat model of transient focal cerebral ischaemia and reperfusion[2].
Venlafaxine is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class.Target: SNRIVenlafaxine is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class. First introduced by Wyeth in 1993, now marketed by Pfizer, it is licensed for the treatment of major depressive disorder (MDD), as a treatment for generalized anxiety disorder, and comorbid indications in certain anxiety disorders with depression. In 2007, venlafaxine was the sixth most commonly prescribed antidepressant on the U.S. retail market, with 17.2 million prescriptions.Venlafaxine is a bicyclic antidepressant, and usually categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI), but it has been referred to as a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI). It works by blocking the transporter "reuptake" proteins for key neurotransmitters affecting mood, thereby leaving more active neurotransmitters in the synapse. The neurotransmitters affected are serotonin and norepinephrine. Additionally, in high doses it weakly inhibits the reuptake of dopamine, with recent evidence showing that the norepinephrine transporter also transports some dopamine as well, since dopamine is inactivated by norepinephrine reuptake in the frontal cortex. The frontal cortex largely lacks dopamine transporters; therefore, venlafaxine can increase dopamine neurotransmission in this part of the brain. Venlafaxine interacts with opioid receptors (mu-, kappa1- kappa3- and delta-opioid receptor subtypes) as well as the alpha2-adrenergic receptor, and was shown to increase pain threshold in mice. When mice were tested with a hotplate analgesia meter (to measure pain), both venlafaxine and mirtazapine induced a dose-dependent, naloxone-reversible antinociceptive effect following intraperitoneal injection. These findings suggest venlafaxine's seemingly superior efficacy in severe depression as narcotics become increasingly used as a measure of last resort for refractory cases.
KN-93 hydrochloride is a cell-permeable, reversible and competitive inhibitor calmodulin-dependent kinase type II (CaMKII) with a Ki of 370 nM.
LY266097 hydrochloride is a selective 5-HT2B receptor antagonist with pKis of 7.7, 9.8, and 7.6 for 5-HT2A, 5-HT2B, 5-HT2C, respectively. 5-HT2B receptor blockade contributes to the research in depression[1].
Ensaculin free base (KA-672) is a NMDA antagonist and have high affinities to serotonergic 5-HT1A and 5-HT7 receptors, adrenergic α1, and dopaminergic D2 and D3 receptors. Ensaculin free base is a memory-enhancing agent. Ensaculin free base has the potential as an antidementia agent acting on various transmitter systems[1].
αO-Conotoxin GeXIVA is a potent α9α10 nAChR antagonist with an IC50 of 12 nM against rat α9α10. αO-Conotoxin GeXIVA shows analgesic in animal models of pain[1].
Cariprazine hydrochloride is a novel antipsychotic drug candidate that exhibits high affinity for the D3 (Ki=0.085 nM) and D2 (Ki=0.49 nM) receptors, and moderate affinity for the 5-HT1A receptor (Ki=2.6 nM).
Granisetron is a serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy.IC50 Value: 17uM (GR reduced 5-HT-evoked contractions) [1]Target: 5-HT3 receptorin vitro: In rat forestomach GR reduced 5-HT-evoked contractions at IC50 17 /- 6 uM. In isolated rabbit heart, GR 0.003-0.03 nM dose-dependently reduced s-HT tachycardia; at high levels GR reduced submaximal and maximal responses to 5-HT [1].in vivo: Leukocyte accumulation was dose-dependently inhibited by granisetron both at 6 and 72 h after induction of inflammation. Granisetron increased PGE(2) level at a lower dose (50 microg/pouch) but higher doses (100 and 200 microg/pouch) inhibited the release. At the same time, TNFalpha production was decreased by the lower dose and increased by higher doses of granisetron in a reciprocal fashion [2]. The GTDS displayed non-inferiority to oral granisetron: complete control was achieved by 60% of patients in the GTDS group, and 65% in the oral granisetron group (treatment difference, -5%; 95% confidence interval, -13-3). Both treatments were well tolerated, the most common adverse event being constipation [3].Clinical trial: Effect of External Heat on a Transdermal Granisetron Patch in Pharmacokinetics (PK) of Healthy Subjects. Phase 1
Hemokinin 1 (mouse) is a selective agonist of neurokinin-1 receptor, with Ki of 0.175 nM and 560 nM for human NK1 receptor and human NK2 receptor, respectively.
DPI-3290 (Org 41793) is a potent and specific opioid receptors agonist with Ki values of 0.18 nM, 0.46 nM, and 0.62 nM for δ-, μ-, and κ-opioid receptors, respectively。DPI-3290 is one of a series of novel centrally acting agents with potent antinociceptive activity[1].
Echimidine N-oxide, a pyrrolizidine alkaloid, has acetylcholinesterase (AChE) inhibitory activity (IC50=0.347 mM)[1].
Cevimeline (Evoxac) Hcl is a parasympathomimetic and muscarinic agonist, with particular effect on M3 receptors; used in the treatment of dry mouth associated with sjogren's syndrome.IC50 value:Target: M3 receptor
Masupirdine mesylate (SUVN-502 mesylate) is a potent, selective, orally bioavailable, and brain penetrant 5-HT6 receptor antagonist (Ki of 2.04 nM for human 5-HT6 receptor). Masupirdine mesylate (SUVN-502 mesylate) shows high selectivity over 5-HT2A receptor and other 100 target sites, and has potential for treatment of Alzheimer's disease[1].
Nociceptin, a heptadecapeptide, is the endogenous ligand of the nociceptin receptor, acting as a potent anti-analgesic.
Sertraline hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class.Target: SSRISertraline is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It was introduced to the market by Pfizer in 1991. Sertraline is primarily prescribed for major depressive disorder in adult outpatients as well as obsessive–compulsive, panic, and social anxiety disorders in both adults and children. In 2011, it was the second-most prescribed antidepressant on the U.S. retail market, with 37,208,000 prescriptions.Sertraline is used for a number of conditions including: major depression, obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), posttraumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), panic disorder and social phobia (social anxiety disorder). It has also been used for premature ejaculation and vascular headaches but evidence of the effectiveness in treating those conditions is less robust.
DMCM (hydrochloride) is Benzodiazepine inverse agonist that displays anxiogenic and potent convulsant activity.The reference for administration is ranging 0.4 from 0.8 mg/kg .DMCM (hydrochloride) was shown to bind to GABAA/benzodiazepine receptors in the rat brain with high affinity.DMCM (hydrochloride) can inhibit pain and learning in rats.
2'-O-Methylisoliquiritigenin, isolated from the Arachis species, up-regulates 5-HT, NE, DA and GABA pathways, but does not put a very significant effect on ne NE pathway[1].
[D-Ala2]leucine-enkephalin, a delta opioid agonist, is a degradation resistant long-acting Leu-enkephalin. Sequence: Tyr-D-Ala-Gly-Phe-Leu.
Pyridostigmine is a parasympathomimetic and a reversible cholinesterase inhibitor.Target: AChEPyridostigmine is a parasympathomimetic and a reversible cholinesterase inhibitor. Since it is a quaternary amine, it is poorly absorbed in the gut and does not cross the blood–brain barrier, except possibly in stressful conditions. Pyridostigmine inhibits acetylcholinesterase in the synaptic cleft, thus slowing down the hydrolysis of acetylcholine. It is a quaternary carbamate inhibitor of cholinesterase that does not cross the blood–brain barrier which carbamylates about 30% of peripheral cholinesterase enzyme. The carbamylated enzyme eventually regenerates by natural hydrolysis and excess ACh levels revert to normal.Pyridostigmine is used to treat muscle weakness in people with myasthenia gravis and to combat the effects of curariform drug toxicity. Pyridostigmine bromide has been FDA approved for military use during combat situations as an agent to be given prior to exposure to the nerve agent Soman in order to increase survival. Used in particular during the first Gulf War, pyridostigmine bromide has been implicated as a causal factor in Gulf War syndrome. Pyridostigmine sometimes is used to treat orthostatic hypotension. It may also be of benefit in chronic axonal polyneuropathy.
Senktide is a tachykinin NK3 receptor agonist.
Miltirone is a natural compound present in the root of Salvia miltiorrhiza. Miltirone is a central benzodiazepine receptor partial agonist, with an IC50 of 0.3 μM[1].
CAD-031 (CAD31) is a novel brain penetrant, J147-derivative that has enhanced neurogenic activity over J147 in human neural precursor cells (NPCs); also stimulates the division of NPCs in the subventricular zone of old APPswe/PS1ΔE9 mice; rescues primary cortical neurons from oxytosis, and effectively reduce oxidative stress with EC50 of 20 nM; also prevents loss of energy metabolism that leads to neuron cell death in an in vitro ischemia model with EC50 of 47 nM; target fatty acid metabolism and inflammation, exhibits therapeutic efficacy on cognitive and physiological parameters in mouse model of AD .
(±)-Anatoxin A fumarate is a natural alkaloid isolated from freshwater cyanobacterium.(±)-Anatoxin A fumarate is a potent nicotinic receptor agonist and exhibits Ki values of 1.25 nM and 1.84 μM for binding to putative α4β2-type nAChR and α7-type nAChR in rat brain membranes, respectively. (±)-Anatoxin A fumarate stimulates [3H]-dopamine release from rat striatal synaptosomes (EC50=134 nM)[1].
Terodiline is an M1-selective muscarinic receptor (mAChR) antagonist with Kbs of 15, 160, 280, and 198 nM in rabbit vas deferens (M1), atria (M2), bladder (M3) and ileal muscle (M3), respectively. Terodiline also is a Ca2+ blocker. Terodiline acts as a treatment for urinary frequency and urge incontinence[1].
NMDA is a specific agonist for NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor.
Serlopitant is a selective Neurokinin-1 (NK-1) receptor antagonist.
γ-Neuropeptide (rabbit) can be isolated from rabbit intestine. γ-Neuropeptide is an endogenous neurokinin peptide that acts as a neurokinin 2 (NK2) receptor agonist. γ-Neuropeptide mediates hypothalamic-pituitary-adrenal (HPA) axis, as well as reproductive hormone release[1][2][3].
MK-3207 is a potent and orally bioavailable CGRP receptor antagonist (IC50= 0.12 nM; Ki value= 0.024 nM); highly selective versus human AM1, AM2, CTR, and AMY3.IC50 Value: 0.024 nM (Ki, Human CGRP) [1]In common with other CGRP receptor antagonists, MK-3207 displays lower affinity for human CGRP receptors from other species, including canine and rodent.in vitro: MK-3207 is a potent antagonist of the human and rhesus monkey CGRP receptors (K(i) = 0.024 nM). in vivo: MK-3207 produced a concentration-dependent inhibition of dermal vasodilation, with plasma concentrations of 0.8 and 7 nM required to block 50 and 90% of the blood flow increase, respectively. The tritiated analog [3H]MK-3207 was used to study the binding characteristics on the human CGRP receptor. [3H]MK-3207 displayed reversible and saturable binding (K(D) = 0.06 nM), and the off-rate was determined to be 0.012 min(-1), with a t(1/2) value of 59 min [1]. After the first interim analysis, the two lowest MK-3207 doses (2.5, 5?mg) were identified as showing insufficient efficacy. Per the pre-specified adaptive design decision rule, only the 2.5-mg group was discontinued and the five highest doses (5, 10, 20, 50, 100?mg) were continued into the second stage [2].Clinical trial: MK-3207 for the treatment of acute migraines. Phase 2b
Protriptyline (N-Methyl-d3) hydrochloride is the deuterium labeled Protriptyline hydrochloride. Protriptyline hydrochloride is a tricyclic antidepressant (TCA), specifically a secondary amine, for the treatment of depression and ADHD. Unique among the TCAs, protriptyline tends to be energizing instead of sedating, used for narcolepsy to achieve a wakefulness-promoting effect[1].
Picraline is a natural alkaloid that targets opioid receptors with binding affinities with Ki values of 132 μM, 2.38 μM and 98.8 μM for μOR, κOR and δOR, respectively[1].