Ketamine Wikipedia

As with their precursors ketamine and norketamine, HNK and DHNK are of great interest to pharmacologists for their putative anti-depressant and analgesic properties. 2-FDCK can be synthesized in a five-step reaction process.1 First 2-fluorobenzonitrile reacts with the Grignard reagent cyclopentyl magnesium bromide followed by a bromination reaction to obtain α-bromocyclopentyl-(2-fluorophenyl)-ketone. The reaction of the obtained ketone with methylamine at -40 °C then results in the formation of α-hydroxycyclopentyl-(2-fluorophenyl)-N-methylamine.

Treatment-resistant depression

Ketamine is legally used in medicine but is also tightly controlled due to its potential for recreational use and dissociative effects. Ketamine is used as a recreational drug for its hallucinogenic and dissociative effects.22 When used recreationally, it is found both in crystalline powder and liquid form, and is often referred to by users as “Ket”, “Special K” or simply “K”. The long-term effects of repeated use are largely unknown and are an area of active investigation.232425 Liver and urinary toxicity have been reported among regular users of high doses of ketamine for recreational purposes.26 Ketamine can cause dissociation and nausea, and other adverse effects, and is contraindicated in severe heart or liver disease, uncontrolled psychosis. Ketamine’s effects are enhanced by propofol, midazolam, and naltrexone; reduced by lamotrigine, nimodipine, and clonidine; and benzodiazepines may blunt its antidepressant action. The use of ketamine as an antidepressant has mainly been studied for the treatment of treatment-resistant depression(TRD).

The illicit market produced new forms of the drug, available as powder, capsules, crystal rocks, tablets, and injectable solutions. 2-Fluorodeschloroketamine (also known as 2′-Fl-2-Oxo-PCM, Fluoroketamine and 2-FDCK) is a dissociative anesthetic1 related to ketamine. Its sale and use as a designer drug has been reported in various countries.234 It is an analogue of ketamine where the chlorine group has been replaced by fluorine. Due to its recent emergence, the pharmacological specifics of the compound are mostly unclear, but effects are reported to be similar to its parent compound, ketamine.

Anesthesia

As it can have severe side effects, it is usually not available as an over-the-counter drug. The synthesis of 2-FDCK was first described in a 2013 paper as part of a larger effort to synthesize and evaluate new anesthetic drugs based on ketamine and its analogues.1 Ketamine itself was first introduced in 1964 and was approved for clinical use in 1970. Since then it has become one of the most important and applicable general anesthetics as well as a popular recreational drug. Ketamine was developed in 1962 as a rapid-acting dissociative anesthetic that was used in surgery. It was approved for human use by the Food and Drug Administration in 1970. Unfortunately, abuse began along the West Coast and spread across the country by the 1980s.

Active mechanisms

• Ketamine’s effects are enhanced by propofol, midazolam, and naltrexone; reduced by lamotrigine, nimodipine, and clonidine; and benzodiazepines may blunt its antidepressant action.
• Unfortunately, abuse began along the West Coast and spread across the country by the 1980s.
• 2-FDCK has an o-fluorophenyl group as an aryl substituent and the amine group is methylated.
• Sometimes it can lead to a special type of hallucination which makes people feel detached,2 which is why some people use it as a recreational drug.
• 2-FDCK belongs to a class of compounds called arylcyclohexylamines which contains various other drugs such as PCP and ketamine.

The use of 2-FDCK as a research chemical has been reported in various countries.256 Many of these new psychoactive substances (NPS) appear on the drug market in order to circumvent existing drug policies. 2-FDCK was first formally notified by the EMCDDA in 2016, alongside 65 other new substances.6 Due to its recent appearance, little research has been done on the compound so far. While most research has historically focused on its precursor, researchers have taken notice of norketamine’s putative effects.

Urinary tract effects

It is a type of drug a doctor might give to put someone to sleep for an operation. Ketamine can also be used as a painkiller and a bronchodilator (which makes it easier for air to get into the lungs).1 In some countries it is used as an analgesic, for fast pain relief such as in bone fractures and in children. It has been or is starting to be used for pain relief both as a replacement for or use with opiates such as morphine with varing success. 2-FDCK is structurally similar to ketamine, so a similar mechanism of action is expected,10 but there has been no study done to confirm this. Due to the halogen in the 2 position not being a chlorine but a fluorine, the molecule is more polar.3 This could influence binding to proteins, such as the NMDA receptor that ketamine primarily binds to and acts as an antagonist towards.

• As it can have severe side effects, it is usually not available as an over-the-counter drug.
• The use of 2-FDCK as a research chemical has been reported in various countries.256 Many of these new psychoactive substances (NPS) appear on the drug market in order to circumvent existing drug policies.
• Finally, the five-membered ring cyclopentanol form is expanded to a cyclohexylketone form by a thermal rearrangement reaction.
• Ketamine was developed in 1962 as a rapid-acting dissociative anesthetic that was used in surgery.
• 2-FDCK has an o-fluorophenyl group as an aryl substituent and the amine group is methylated.

Finally, the five-membered ring cyclopentanol form is expanded to a cyclohexylketone form by a thermal rearrangement reaction. Drug Enforcement Administration conducted Operation TKO, a probe into the quality of ketamine being imported from Mexico.63 As a result of operation TKO, U.S. and Mexican authorities shut down the Mexico City company Laboratorios Ttokkyo, which was the biggest producer of ketamine in Mexico. According to the DEA, over 80% of ketamine seized in the United States is of Mexican origin. As of 2011, it was mostly shipped from places like India, as cheap in cost as $5/gram.63 The World Health Organization Expert Committee on Drug Dependence, in its thirty-third report (2003),64 recommended research into ketamine’s recreational use due to growing concerns about its rising popularity in Europe, Asia, and North America.

At lower, sub-anesthetic doses, it is used as a treatment for pain and treatment-resistant depression. Much of the research examining the potential role of norketamine as a distinct anti-depressant to its precursor began in the mid-2010s. It is a drug of choice for short-term procedures when muscle relaxation is not required.32 The effect of ketamine on the respiratory and circulatory systems is different from that of other anesthetics.

Relationships between levels and effects

Single-dose use has been found to have noticeable and rapid anti-depressive effects that tend to last up to a week, accompanied by acute side-effects that resolve spontaneously.26 It has also been shown to have a moderate-to-large effect in reducing suicidality in some patients suffering from suicidal ideation,27 with visible efficacy within two hours of administration. This is in sharp contrast with currently-approved treatment options, whose delayed onset poses an increased risk for suicidality in patients. However, this potency cannot currently be generalised for non-depressed patients experiencing suicidal ideation.

Beginning in the late 1990s, Danish researchers discovered its role as a NMDA receptor antagonist. Later research uncovered its use as an antinociceptive, or “painkiller.” A study (from 2012) used monkeys as a model to see if ketamine is toxic to the brain.11The study found that injecting the monkeys every day for 6 months with ketamine caused more cells to die in the front of their brain and also caused a decrease in activity in the areas of the brain which control movement. 2-FDCK belongs to a class of compounds called arylcyclohexylamines which contains various other drugs such as PCP and ketamine. Their general structure consists of a cyclohexylamine unit with an aryl group attached to the same carbon as the amine. 2-FDCK has an o-fluorophenyl group as an aryl substituent and the amine group is methylated.

Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties, used medically for anesthesia, depression, and pain management.1920 Ketamine exists as its two enantiomers, S- (esketamine) and R- (arketamine), and has antidepressant action likely involving additional mechanisms than NMDA antagonism. Following the 2019 approval of the ketamine enantiomer esketamine by the European Medicines Agency and FDA for use with treatment-resistant depression, researchers and pharmaceutical companies have sought other effective intermediates and metabolites of racemic ketamine. The profile of these side effects are generally the opposite of morphine, but the dose of ketamine is lower than a recreational dose and it is not usually enough to cause a high. Sometimes ketamine wikipedia it can lead to a special type of hallucination which makes people feel detached,2 which is why some people use it as a recreational drug.