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ACD856
ACD856, or ACD-856, is a tropomyosin receptor kinase TrkA, TrkB, and TrkC positive allosteric modulator which is under development for the treatment of Alzheimer's disease, depressive disorders, sleep disorders, and traumatic brain injuries. It is taken by mouth. Pharmacology The drug potentiates the tropomyosin receptor kinases TrkA, TrkB, and TrkC with values of 382nM, 295nM, and ~330nM, respectively. As a positive allosteric modulator of TrkA and TrkB, ACD856 potentiates the effects of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). In addition to the tropomyosin receptor kinases, ACD856 is also a similarly potent positive allosteric modulator of certain other receptor tyrosine kinases, including the insulin-like growth factor 1 receptor (IGF1R) and the fibroblast growth factor receptor 1 (FGFR1). However, its efficacies at the IGF1R and FGFR1 were much lower than at the TrkA, TrkB, and TrkC. In animals, ACD856 has been found to reverse scopola ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tropomyosin Receptor Kinase A
Tropomyosin receptor kinase A (TrkA), also known as high affinity nerve growth factor receptor, neurotrophic tyrosine kinase receptor type 1, or TRK1-transforming tyrosine kinase protein is a protein that in humans is encoded by the ''NTRK1'' gene. This gene encodes a member of the neurotrophic tyrosine kinase receptor (NTKR) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself (autophosphorylation) and members of the MAPK pathway. The presence of this kinase leads to cell differentiation and may play a role in specifying sensory neuron subtypes. Mutations in this gene have been associated with congenital insensitivity to pain with anhidrosis, self-mutilating behaviors, intellectual disability and/or cognitive impairment and certain cancers. Alternate transcriptional splice variants of this gene have been found, but only three have been characterized to date. Function and Interaction with NGF TrkA is the high affinity cataly ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tropomyosin Receptor Kinase B
Tropomyosin receptor kinase B (TrkB), also known as tyrosine receptor kinase B, or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the ''NTRK2'' gene. TrkB is a receptor for brain-derived neurotrophic factor (BDNF). The standard pronunciation for this protein is "track bee". Function Tropomyosin receptor kinase B is the high affinity catalytic receptor for several "neurotrophins", which are small protein growth factors that induce the survival and differentiation of distinct cell populations. The neurotrophins that activate TrkB are: BDNF (Brain Derived Neurotrophic Factor), neurotrophin-4 (NT-4), and neurotrophin-3 (NT-3). As such, TrkB mediates the multiple effects of these neurotrophic factors, which includes neuronal differentiation and survival. Research has shown that activation of the TrkB receptor can lead to down regulation of the KCC2 chloride transporter in cells of the CNS. In additio ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TrkA
Tropomyosin receptor kinase A (TrkA), also known as high affinity nerve growth factor receptor, neurotrophic tyrosine kinase receptor type 1, or TRK1-transforming tyrosine kinase protein is a protein that in humans is encoded by the ''NTRK1'' gene. This gene encodes a member of the neurotrophic tyrosine kinase receptor (NTKR) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself ( autophosphorylation) and members of the MAPK pathway. The presence of this kinase leads to cell differentiation and may play a role in specifying sensory neuron subtypes. Mutations in this gene have been associated with congenital insensitivity to pain with anhidrosis, self-mutilating behaviors, intellectual disability and/or cognitive impairment and certain cancers. Alternate transcriptional splice variants of this gene have been found, but only three have been characterized to date. Function and Interaction with NGF TrkA is the high affinity catal ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oral Administration
Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administration can be easier and less painful than other routes of administration, such as Injection (medicine), injection. However, the onset of action is relatively low, and the effectiveness is reduced if it is not absorbed properly in the digestive system, or if it is broken down by digestive enzymes before it can reach the bloodstream. Some medications may cause gastrointestinal side effects, such as nausea or vomiting, when taken orally. Oral administration can also only be applied to conscious patients, and patients able to swallow. Terminology ''Per os'' (; ''P.O.'') is an adverbial phrase meaning literally from Latin "through the mouth" or "by mouth". The expression is used in medicine to describe a treatment that is taken orally (but not ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Memory Impairment
Amnesia is a deficit in memory caused by brain damage or brain diseases,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be temporarily caused by the use of various sedative and hypnotic drugs. The memory can be either wholly or partially lost due to the extent of damage that is caused. There are two main types of amnesia: * Retrograde amnesia is the inability to remember information that was acquired before a particular date, usually the date of an accident or operation. In some cases, the memory loss can extend back decades, while in other cases, people may lose only a few months of memory. * Anterograde amnesia is the inability to transfer new information from the short-term store into the long-term store. People with anterograde amnesia cannot remember things for long periods of time. These two types are not mutually exclusive; both can also occur simultaneously. Case studi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Intrinsic Activity
Intrinsic activity (IA) and efficacy (Emax) refer to the relative ability of a drug- receptor complex to produce a maximum functional response. This must be distinguished from the affinity, which is a measure of the ability of the drug to bind to its molecular target, and the EC50, which is a measure of the potency of the drug and which is proportional to both efficacy and affinity. This use of the word "efficacy" was introduced by Stephenson (1956) to describe the way in which agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...s vary in the response they produce, even when they occupy the same number of receptors. High efficacy agonists can produce the maximal response of the receptor system while occupying a relatively low proportion of the receptors in that system. Th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Scopolamine
Scopolamine, also known as hyoscine, or Devil's Breath, is a medication used to treat motion sickness and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva. When used by injection, effects begin after about 20 minutes and last for up to 8 hours. It may also be used orally and as a transdermal patch since it has been long known to have transdermal bioavailability. Scopolamine is in the antimuscarinic family of drugs and works by blocking some of the effects of acetylcholine within the nervous system. Scopolamine was first written about in 1881 and started to be used for anesthesia around 1900. Scopolamine is also the main active component produced by certain plants of the nightshade family, which historically have been used as psychoactive drugs, known as '' deliriants'', due to their antimuscarinic-induced hallucinogenic effects in higher doses. In these contexts, its mind-altering effects have been utilized for recre ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dizocilpine
Dizocilpine ( INN), also known as MK-801, is a pore blocker of the NMDA receptor, a glutamate receptor, discovered by a team at Merck in 1982. Glutamate is the brain's primary excitatory neurotransmitter. The channel is normally blocked with a magnesium ion and requires depolarization of the neuron to remove the magnesium and allow the glutamate to open the channel, causing an influx of calcium, which then leads to subsequent depolarization. Dizocilpine binds inside the ion channel of the receptor at several of PCP's binding sites thus preventing the flow of ions, including calcium (Ca2+), through the channel. Dizocilpine blocks NMDA receptors in a use- and voltage-dependent manner, since the channel must open for the drug to bind inside it. The drug acts as a potent anti-convulsant and probably has dissociative anesthetic properties, but it is not used clinically for this purpose because of the discovery of brain lesions, called Olney's lesions (see below), in laboratory rats. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Memory Deficit
Amnesia is a deficit in memory caused by brain damage or brain diseases,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be temporarily caused by the use of various sedative and hypnotic drugs. The memory can be either wholly or partially lost due to the extent of damage that is caused. There are two main types of amnesia: * Retrograde amnesia is the inability to remember information that was acquired before a particular date, usually the date of an accident or operation. In some cases, the memory loss can extend back decades, while in other cases, people may lose only a few months of memory. * Anterograde amnesia is the inability to transfer new information from the short-term store into the long-term store. People with anterograde amnesia cannot remember things for long periods of time. These two types are not mutually exclusive; both can also occur simultaneously. Case studie ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Aging
Ageing (or aging in American English) is the process of becoming Old age, older until death. The term refers mainly to humans, many other animals, and fungi; whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In a broader sense, ageing can refer to single cells within an organism which have Cellular senescence, ceased dividing, or to the Population ageing, population of a species. In humans, ageing represents the accumulation of changes in a human being over time and can encompass physical, psychological, and social changes. Reaction time, for example, may slow with age, while memories and general knowledge typically increase. Of the roughly 150,000 people who die each day across the globe, about two-thirds die from age-related causes. Current Theory of aging, ageing theories are assigned to the damage concept, whereby the accumulation of damage (such as DNA oxidation) may cause biological systems to fail, or to the p ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Insulin-like Growth Factor 1 Receptor
The insulin-like growth factor 1 (IGF-1) receptor is a protein found on the surface of human cells. It is a transmembrane receptor that is activated by a hormone called insulin-like growth factor 1 ( IGF-1) and by a related hormone called IGF-2. It belongs to the large class of tyrosine kinase receptors. This receptor mediates the effects of IGF-1, which is a polypeptide protein hormone similar in molecular structure to insulin. IGF-1 plays an important role in growth and continues to have anabolic effects in adults – meaning that it can induce hypertrophy of skeletal muscle and other target tissues. Mice lacking the IGF-1 receptor die late in development, and show a dramatic reduction in body mass. This testifies to the strong growth-promoting effect of this receptor. Structure Two alpha subunits and two beta subunits make up the IGF-1 receptor. Both the α and β subunits are synthesized from a single mRNA precursor. The precursor is then glycosylated, proteolyticall ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
