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Hydroxynorketamine
Hydroxynorketamine (HNK), or 6-hydroxynorketamine, is a minor metabolite of the anesthetic, dissociative, and antidepressant drug ketamine. It is formed by hydroxylation of the intermediate norketamine, another metabolite of ketamine. As of late 2019, (2''R'',6''R'')-HNK is in clinical trials for the treatment of depression. The major metabolite of ketamine is norketamine (80%). Norketamine is secondarily converted into 4-, 5-, and 6-hydroxynorketamines (15%), mainly HNK (6-hydroxynorketamine). Ketamine is also transformed into hydroxyketamine (5%). As such, bioactivated HNK comprises less than 15% of a dose of ketamine. Pharmacology In contrast to ketamine and norketamine, HNK is inactive as an anesthetic and psychostimulant. In accordance, it has only very weak affinity for the NMDA receptor (Ki = 21.19 μM and > 100 μM for (2''S'',6''S'')-HNK and (2''R'',6''R'')-HNK, respectively). However, HNK does still show biological activity, having been found to act as a potent and s ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Norketamine
Norketamine, or ''N''-desmethylketamine, is the major active metabolite of ketamine, which is formed mainly by CYP3A4. Similarly to ketamine, norketamine acts as a noncompetitive NMDA receptor antagonist, but is about 3–5 times less potent as an anesthetic in comparison. Pharmacology Pharmacodynamics Similarly to ketamine, norketamine acts as a noncompetitive NMDA receptor antagonist (Ki = 1.7μM and 13μM for (''S'')-(+)-norketamine and (''R'')-(–)-norketamine, respectively). Also, similarly again to ketamine, norketamine binds to the μ- and κ-opioid receptors. Relative to ketamine, norketamine is much more potent as an antagonist of the α7-nicotinic acetylcholine receptor, and produces rapid antidepressant effects in animal models which have been reported to correlate with its activity at this receptor. However, norketamine is about 1/5 as potent as ketamine as an antidepressant in mice as per the forced swim test, and this seems also to be in accordance with i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Ketamine
Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties, used medically for anesthesia, depression, and pain management. Ketamine exists as its S- (esketamine) and R- (arketamine) two enantiomers and has antidepressant action likely involving additional mechanisms than NMDA antagonism. At anesthetic doses, ketamine induces a state of dissociative anesthesia, a trance-like state providing pain relief, sedation, and amnesia. Its distinguishing features as an anesthestic are preserved breathing and airway reflexes, stimulated heart function with increased blood pressure, and moderate bronchodilation. As an anesthetic, it is used especially in trauma, Emergency medical services, emergency, and Pediatrics, pediatric cases. At lower, sub-anesthetic doses, it is used as a treatment for pain and treatment-resistant depression. Ketamine is legally used in medicine but is also tightly controlled due to ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Dehydronorketamine
Dehydronorketamine (DHNK), or 5,6-dehydronorketamine, is a minor metabolite of ketamine which is formed by dehydrogenation of its metabolite norketamine. Though originally considered to be inactive, DHNK has been found to act as a potent and selective negative allosteric modulator of the α7-nicotinic acetylcholine receptor ( IC50 = 55 nM). For this reason, similarly to hydroxynorketamine (HNK), it has been hypothesized that DHNK may have the capacity to produce rapid antidepressant effects. However, unlike ketamine, norketamine, and HNK, DHNK has been found to be inactive in the forced swim test (FST) in mice at doses up to 50 mg/kg. DHNK is inactive at the α3β4-nicotinic acetylcholine receptor (IC50 > 100 μM) and is only very weakly active at the NMDA receptor (Ki = 38.95 μM for (''S'')-(+)-DHNK). It can be detected 7–10 days after a modest dose of ketamine, and because of this, is useful in drug detection assays. See also * Arketamine * Esketamine Esketam ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
IC50
Half maximal inhibitory concentration (IC50) is a measure of the potency of a substance in inhibiting a specific biological or biochemical function. IC50 is a quantitative measure that indicates how much of a particular inhibitory substance (e.g. drug) is needed to inhibit, ''in vitro'', a given biological process or biological component by 50%. The biological component could be an enzyme, cell, cell receptor or microbe. IC50 values are typically expressed as molar concentration. IC50 is commonly used as a measure of antagonist drug potency in pharmacological research. IC50 is comparable to other measures of potency, such as EC50 for excitatory drugs. EC50 represents the dose or plasma concentration required for obtaining 50% of a maximum effect ''in vivo''. IC50 can be determined with functional assays or with competition binding assays. Sometimes, IC50 values are converted to the pIC50 scale. :\ce = -\log_ \ce Due to the minus sign, higher values of pIC50 indicate ex ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
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] [Amazon] |
AMPA Receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic glutamate receptor (iGluR) and predominantly sodium ion channel that mediates fast excitatory neurotransmission in the Central nervous system, central nervous system (CNS). Its activation by the neurotransmitter Glutamate (neurotransmitter), glutamate facilitates rapid neuronal communication, essential for various brain functions, including learning and memory. Its name is derived from the ability to be activated by the artificial glutamate analog AMPA. The receptor was initially named the "Quisqualic acid, quisqualate receptor" by Watkins and colleagues after the naturally occurring agonist quisqualic acid, quisqualate. Later, the receptor was designated as the "AMPA receptor" following the development of the selective agonist AMPA by Tage Honore and colleagues at the Royal Danish School of Pharmacy in Copenhagen. The ''GRIA2''- ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Traxoprodil
Traxoprodil (developmental code name CP-101606) is a drug developed by Pfizer which acts as an NMDA antagonist, selective for the NR2B subunit. It has neuroprotective, analgesic, and anti-Parkinsonian effects in animal studies. Traxoprodil has been researched in humans as a potential treatment to lessen the damage to the brain after stroke, but results from clinical trials showed only modest benefit. The drug was found to cause EKG abnormalities (QT prolongation) and its clinical development was stopped. More recent animal studies have suggested traxoprodil may exhibit rapid-acting antidepressant effects similar to those of ketamine, although there is some evidence for similar psychoactive side effects and abuse potential at higher doses, which might limit clinical acceptance of traxoprodil for this application. Traxoprodil showed ketamine-like rapidly-acting antidepressant effects in a small clinical trial of 30 patients with depression who were non-responders to 6 w ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Lanicemine
Lanicemine (AZD6765) is a low-trapping NMDA receptor antagonist that was under drug development, development by AstraZeneca for the management of severe and treatment-resistant depression. Lanicemine differs from ketamine in that it is a ''low-trapping'' NMDA receptor antagonist, showing similar rapid-acting antidepressant effects to ketamine in clinical trials but with little or no psychotomimetic side effects. However, lanicemine did not meet study endpoints, and its development was terminated by AstraZeneca in 2013. See also * 4-Chlorokynurenine * AD-1211 * Apimostinel * CERC-301 * Diphenidine * Ephenidine * Esketamine * Lefetamine * Memantine * Methoxphenidine * MT-45 * Rapastinel References {{Ionotropic glutamate receptor modulators Abandoned drugs Phenyl compounds NMDA receptor antagonists 1,2-Diarylethylamines 2-Pyridyl compounds ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Memantine
Memantine, sold under the brand name Namenda among others, is a medication used to slow the progression of moderate-to-severe Alzheimer's disease. It is taken by mouth. Common side effects include headache, constipation, sleepiness, and dizziness. Severe side effects may include blood clots, psychosis, and heart failure. It is believed to work by acting on NMDA receptors, working as a pore blocker of these ion channels. Memantine was first discovered in 1963. It was approved for medical use in Germany in 1989, in the European Union in 2002, and in the United States in 2003. It is available as a generic medication. In 2022, it was the 150th most commonly prescribed medication in the United States, with more than 3million prescriptions. Medical uses Alzheimer's disease and dementia Memantine is used to treat moderate-to-severe Alzheimer's disease, especially for people who are intolerant of or have a contraindication to AChE (acetylcholinesterase) inhibitors.NICE review ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
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] [Amazon] |
Nature (journal)
''Nature'' is a British weekly scientific journal founded and based in London, England. As a multidisciplinary publication, ''Nature'' features Peer review, peer-reviewed research from a variety of academic disciplines, mainly in science and technology. It has core editorial offices across the United States, continental Europe, and Asia under the international scientific publishing company Springer Nature. ''Nature'' was one of the world's most cited scientific journals by the Science Edition of the 2022 ''Journal Citation Reports'' (with an ascribed impact factor of 50.5), making it one of the world's most-read and most prestigious academic journals. , it claimed an online readership of about three million unique readers per month. Founded in the autumn of 1869, ''Nature'' was first circulated by Norman Lockyer and Alexander MacMillan (publisher), Alexander MacMillan as a public forum for scientific innovations. The mid-20th century facilitated an editorial expansion for the j ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
