|
Rapastinel
Rapastinel () (former developmental code name GLYX-13) is a novel antidepressant that was under development by Allergan (previously Naurex) as an adjunctive therapy for the treatment of treatment-resistant depression. It is a centrally active, intravenously administered (non- orally active) amidated tetrapeptide that acts as a novel and selective modulator of the NMDA receptor. The drug is a rapid-acting and long-lasting antidepressant as well as robust cognitive enhancer by virtue of its ability to enhance NMDA receptor-mediated signal transduction and synaptic plasticity. Clinical development On March 3, 2014, the U.S. FDA granted Fast Track designation to the development of rapastinel as an adjunctive therapy in treatment-resistant major depressive disorder. As of 2015, the drug had completed phase II clinical development for this indication and achieved proof of concept as a rapid-acting antidepressant by demonstrating reduced depressive symptoms at days 1 through ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
B6B21
Rapastinel () (former developmental code name GLYX-13) is a novel antidepressant that was under development by Allergan (previously Naurex) as an adjunctive therapy for the treatment of treatment-resistant depression. It is a centrally active, intravenously administered (non- orally active) amidated tetrapeptide that acts as a novel and selective modulator of the NMDA receptor. The drug is a rapid-acting and long-lasting antidepressant as well as robust cognitive enhancer by virtue of its ability to enhance NMDA receptor-mediated signal transduction and synaptic plasticity. Clinical development On March 3, 2014, the U.S. FDA granted Fast Track designation to the development of rapastinel as an adjunctive therapy in treatment-resistant major depressive disorder. As of 2015, the drug had completed phase II clinical development for this indication and achieved proof of concept as a rapid-acting antidepressant by demonstrating reduced depressive symptoms at days 1 through 7, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Apimostinel
__NOTOC__ Apimostinel (GATE-202, formerly NRX-1074) is an investigational antidepressant, acting as a novel and selective modulator of the NMDA receptor. It is currently under development for the acute treatment of major depressive disorder (MDD) by Syndeio Biosciences, and previously by Naurex and Allergan. As of February 2015, an intravenous formulation of apimostinel has completed a phase IIa clinical trial for MDD. Similar to rapastinel (GLYX-13), its mechanism of action acts through a unique binding site on the NMDA receptor, independent of the glycine site, to modulate receptor activity and enhance NMDAR-mediated synaptic plasticity. However, apimostinel is 1000-fold more potent in vitro and is intended as an improved, follow-up drug to rapastinel. Similar to rapastinel, apimostinel is an amidated tetrapeptide, but has been structurally modified, via the addition of a benzyl group, to enhance its metabolic stability and pharmacokinetic profile. The drug has shown rapid a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
NMDA Receptor
The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA receptor, AMPA and kainate receptors. Depending on its subunit composition, its Ligand (biochemistry), ligands are Glutamate (neurotransmitter), glutamate and glycine (or D-Serine, D-serine). However, the binding of the ligands is typically not sufficient to open the channel as it may be blocked by Magnesium, Mg2+ ions which are only removed when the neuron is sufficiently depolarized. Thus, the channel acts as a "coincidence detector" and only once both of these conditions are met, the channel opens and it allows cation, positively charged ions (cations) to flow through the cell membrane. The NMDA receptor is thought to be very important for controlling synaptic plasticity and mediating learning and memory functions. The N ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
AGN-241751
Zelquistinel (GATE-251, formerly AGN-241751) is an orally active small-molecule NMDA receptor modulator which is under development for the treatment of major depressive disorder (MDD) by Syndeio Biosciences, and previously by Allergan. Pharmacology Zelquistinel acts through a unique binding site on the NMDA receptor, independent of the glycine site, to modulate receptor activity and enhance NMDAR-mediated synaptic plasticity. Its mechanism of action is similar to that of rapastinel. However, unlike rapastinel, zelquistinel is orally bioavailable, exhibits increased potency, and has improved drug properties. The mean half-life of Zelquistinel is reported to be from 1.21 to 2.06 hours, reaching peak plasma concentrations 30 minutes after administration. In preclinical studies, single doses of zelquistinel demonstrated both rapid-acting (24-hours) and sustained (1-week) antidepressant-like effects and enhancement of long-term synaptic plasticity. Clinical development On July ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Tetrapeptide
A tetrapeptide is a peptide, classified as an oligopeptide, since it only consists of four amino acids joined by peptide bonds. Many tetrapeptides are pharmacologically active, often showing affinity and specificity for a variety of receptors in protein-protein signaling. Present in nature are both linear and cyclic tetrapeptides (CTPs), the latter of which mimics protein reverse turns which are often present on the surface of proteins and druggable targets. Tetrapeptides may be cyclized by a fourth peptide bond or other covalent bonds. Examples of tetrapeptides are: * Tuftsin (L-threonyl-L-lysyl-L-prolyl-L-arginine) is a peptide related primarily to the immune system function. * Rigin (glycyl-L-glutaminyl-L-prolyl-L-arginine) is a tetrapeptide with functions similar to those of tuftsin. * Postin (Lys-Pro-Pro-Arg) is the N-terminal tetrapeptide of cystatin C and an antagonist of tuftsin. * Endomorphin-1 (H-Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH2) a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Intravenous Administration
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrients for those who cannot, or will not—due to reduced mental states or otherwise—consume food or water per os, by mouth. It may also be used to administer pharmaceutical drug, medications or other medical therapy such as blood transfusion, blood products or electrolytes to correct electrolyte imbalances. Attempts at providing intravenous therapy have been recorded as early as the 1400s, but the practice did not become widespread until the 1900s after the development of techniques for safe, effective use. The intravenous route is the fastest way to deliver medications and fluid replacement throughout the body as they are introduced directly into the circulatory system and thus quickly distributed. For this reason, the intravenous route ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Synaptic Plasticity
In neuroscience, synaptic plasticity is the ability of synapses to Chemical synapse#Synaptic strength, strengthen or weaken over time, in response to increases or decreases in their activity. Since memory, memories are postulated to be represented by vastly interconnected neural circuits in the brain, synaptic plasticity is one of the important neurochemical foundations of learning and memory (''see Hebbian theory''). Plastic change often results from the alteration of the number of neurotransmitter receptors located on a synapse. There are several underlying mechanisms that cooperate to achieve synaptic plasticity, including changes in the quantity of neurotransmitters released into a synapse and changes in how effectively cells respond to those neurotransmitters. Synaptic plasticity in both Excitatory synapse, excitatory and Inhibitory synapse, inhibitory synapses has been found to be dependent upon postsynaptic calcium release. Historical discoveries In 1973, Terje Lømo and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Monoclonal Antibody
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies are identical and can thus have monovalent affinity, binding only to a particular epitope (the part of an antigen that is recognized by the antibody). In contrast, polyclonal antibodies are mixtures of antibodies derived from multiple plasma cell lineages which each bind to their particular target epitope. Artificial antibodies known as bispecific monoclonal antibodies can also be engineered which include two different antigen binding sites ( FABs) on the same antibody. It is possible to produce monoclonal antibodies that specifically bind to almost any suitable substance; they can then serve to detect or purify it. This capability has become an investigative tool in biochemistry, molecular biology, and medicine. Monoclonal antibod ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Structural Modification
Molecular modification is chemical alteration of a known and previously characterized lead compound for the purpose of enhancing its usefulness as a drug. This could mean enhancing its specificity for a particular body target site, increasing its potency, improving its rate and extent of absorption, modifying to advantage its time course in the body, reducing its toxicity, changing its physical or chemical properties (like solubility) to provide desired features. Modification for water solubility Molecular modification is used to enhance drug's water solubility by incorporating water solubilizing groups in its structure. The discussion of the introduction of water solubilizing groups into the structure of a lead compound can be conveniently broken down into four general areas: * The type of group introduced; * Whether the introduction is reversible or irreversible; * The position of incorporation; and * The chemical route of introduction. The type of group The incorporation of p ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Potency (pharmacology)
In pharmacology, potency or biological potency is a measure of a drug's biological activity expressed in terms of the dose required to produce a pharmacological effect of given intensity. A highly potent drug (e.g., fentanyl, clonazepam, risperidone, benperidol, bumetanide) evokes a given response at low concentrations, while a drug of lower potency (e.g. morphine, alprazolam, ziprasidone, haloperidol, furosemide) evokes the same response only at higher concentrations. Higher potency does not necessarily mean greater effectiveness nor more side effects nor less side effects. Types of potency The International Union of Basic and Clinical Pharmacology (IUPHAR) has stated that "potency is an imprecise term that should always be further defined", and lists of types of potency as follows: Miscellaneous Lysergic acid diethylamide (LSD) is one of the most potent psychoactive drug A psychoactive drug, psychopharmaceutical, mind-altering drug, consciousness-altering drug, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Structural Analog
A structural analog, also known as a chemical analog or simply an analog, is a chemical compound, compound having a chemical structure, structure similar to that of another compound, but differing from it in respect to a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced with other atoms, groups, or substructures. A structural analog can be imagined to be formed, at least theoretically, from the other compound. Structural analogs are often isoelectronicity, isoelectronic. Despite a high chemical similarity, structural analogs are not necessarily functional analog (chemistry), functional analogs and can have very different physical, chemical, biochemical, or pharmacological properties. In drug discovery, either a large series of structural analogs of an initial lead compound are created and tested as part of a structure–activity relationship study or a database is virtual screening, screened for structural analogs of a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Breakthrough Therapy
Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "breakthrough therapy" designation is not intended to imply that a drug is actually a "breakthrough" or that there is high-quality evidence of treatment efficacy for a particular condition; rather, it allows the FDA to grant priority review to drug candidates if preliminary clinical trials indicate that the therapy may offer substantial treatment advantages over existing options for patients with serious or life-threatening diseases. The FDA has other mechanisms for expediting the review and approval process for promising drugs, including fast track designation, accelerated approval, and priority review. Requirements A breakthrough therapy designation can be assigned to a drug if "it is a drug which is intended alone or in combination wit ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
