Legal status | |
---|---|
Legal status |
|
Identifiers | |
| |
CAS Number | |
PubChem CID | |
ChemSpider | |
UNII | |
CompTox Dashboard (EPA) | |
Chemical and physical data | |
Formula | C13H16FNO |
Molar mass | 221.275 g·mol−1 |
3D model (JSmol) | |
| |
|
2-Fluorodeschloroketamine (also known as 2'-Fl-2-Oxo-PCM, Fluoroketamine and 2-FDCK) is a dissociative anesthetic [1] related to ketamine. Its sale and use as a designer drug has been reported in various countries. [2] [3] [4] It is an analogue of ketamine where the chlorine group has been replaced by fluorine.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.
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.
The use of 2-FDCK as a research chemical has been reported in various countries. [2] [5] [6] 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.
In January 2023, Israeli Biotech company "Clearmind Medicine Inc." announced the successful completion of a preclinical study examining 2-FDCK in a rat model of depression, with the compound outperforming ketamine in longevity of antidepressant effect. [7]
The full chemical name of 2-FDCK is 2-(2-fluorophenyl)-2-(methylamino)cyclohexan-1-one.
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. The cyclohexyl ring features a ketone group next to the amine position.
The chemical structure of 2-FDCK differs from ketamine only in that there is a fluorine atom attached to the phenyl group. Ketamine has a chlorine atom in that position. [8]
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. Finally, the five-membered ring cyclopentanol form is expanded to a cyclohexylketone form by a thermal rearrangement reaction. HCl is used to create a water-soluble HCl salt of 2-FDCK.
2-FDCK and its metabolites can be detected in urine with the use of liquid chromatography mass spectrometry (LC/MS). [4] [9]
The metabolism of 2-FDCK is analogous to that of ketamine: the enzymes CYP2B6 and CYP3A4, the latter to a lesser extent, metabolise 2-FDCK to Nor-2FDCK via N-demethylation. This is further metabolised either to dehydronor-2FDCK by CYP2B6 or to hydroxynor-2FDCK by CYP2A6 and CYP2B6. [3]
In general, the 2-FDCK equivalent shows stronger docking to CYP2B6 in simulations, as well as slower metabolism rate, than the more well-known ketamine. The lipophilicity is observed to be lower for 2-FDCK than for ketamine. [3] In vitro to in vivo extrapolation predicts that in the body, 2-FDCK shows a lower intrinsic hepatic clearance than ketamine. Both of these characteristics would suggest that the effects of 2-FDCK last longer than those of ketamine. [2]
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.
For general (halogen) substitutions of ketamine, docking strength for CYP2B6 follows the pattern H < Br < Cl < F. The parameter of internal clearance follows the pattern Br > Cl > F > H. Lastly, Km (Michaelis constant) follows the pattern of Br < Cl < F < H, and as such the in-vitro metabolism rate follows the inverse pattern, namely Br > Cl > F > H. [4]
In 2019, 2-FDCK was found in poisoned individuals in Hong Kong in combination with other ketamine-type drugs. [4]
Due to the fast emergence of NPS, new substances such as 2-FDCK are often not yet specifically mentioned in controlled substance legislation. As a result, NPS are sometimes marketed as 'legal highs'. 2-FDCK is currently illegal in Italy [11] Japan, [12] Latvia, [13] Singapore, [14] Sweden, [15] Switzerland, [16] as well as being covered by blanket bans in Canada, [17] Belgium, [18] and the UK. [19]
In October 2023 the ECDD recommended that 2-FDCK be added to Schedule II of the Convention on Psychotropic Substances of 1971. [20]
Bromine is a chemical element; it has symbol Br and atomic number 35. It is a volatile red-brown liquid at room temperature that evaporates readily to form a similarly coloured vapour. Its properties are intermediate between those of chlorine and iodine. Isolated independently by two chemists, Carl Jacob Löwig and Antoine Jérôme Balard, its name was derived from Ancient Greek βρῶμος (bromos) 'stench', referring to its sharp and pungent smell.
Chlorine is a chemical element; it has symbol Cl and atomic number 17. The second-lightest of the halogens, it appears between fluorine and bromine in the periodic table and its properties are mostly intermediate between them. Chlorine is a yellow-green gas at room temperature. It is an extremely reactive element and a strong oxidising agent: among the elements, it has the highest electron affinity and the third-highest electronegativity on the revised Pauling scale, behind only oxygen and fluorine.
The halogens are a group in the periodic table consisting of six chemically related elements: fluorine (F), chlorine (Cl), bromine (Br), iodine (I), and the radioactive elements astatine (At) and tennessine (Ts), though some authors would exclude tennessine as its chemistry is unknown and is theoretically expected to be more like that of gallium. In the modern IUPAC nomenclature, this group is known as group 17.
Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a treatment for depression and in pain management. Ketamine is an NMDA receptor antagonist which accounts for most of its psychoactive effects.
The haloalkanes are alkanes containing one or more halogen substituents. They are a subset of the general class of halocarbons, although the distinction is not often made. Haloalkanes are widely used commercially. They are used as flame retardants, fire extinguishants, refrigerants, propellants, solvents, and pharmaceuticals. Subsequent to the widespread use in commerce, many halocarbons have also been shown to be serious pollutants and toxins. For example, the chlorofluorocarbons have been shown to lead to ozone depletion. Methyl bromide is a controversial fumigant. Only haloalkanes that contain chlorine, bromine, and iodine are a threat to the ozone layer, but fluorinated volatile haloalkanes in theory may have activity as greenhouse gases. Methyl iodide, a naturally occurring substance, however, does not have ozone-depleting properties and the United States Environmental Protection Agency has designated the compound a non-ozone layer depleter. For more information, see Halomethane. Haloalkane or alkyl halides are the compounds which have the general formula "RX" where R is an alkyl or substituted alkyl group and X is a halogen.
In chemistry, halogenation is a chemical reaction which introduces one or more halogens into a chemical compound. Halide-containing compounds are pervasive, making this type of transformation important, e.g. in the production of polymers, drugs. This kind of conversion is in fact so common that a comprehensive overview is challenging. This article mainly deals with halogenation using elemental halogens. Halides are also commonly introduced using salts of the halides and halogen acids. Many specialized reagents exist for and introducing halogens into diverse substrates, e.g. thionyl chloride.
In chemistry, an interhalogen compound is a molecule which contains two or more different halogen atoms and no atoms of elements from any other group.
Organobromine chemistry is the study of the synthesis and properties of organobromine compounds, also called organobromides, which are organic compounds that contain carbon bonded to bromine. The most pervasive is the naturally produced bromomethane.
Arylcyclohexylamines, also known as arylcyclohexamines or arylcyclohexanamines, are a chemical class of pharmaceutical, designer, and experimental drugs.
3-Fluoroamphetamine is a stimulant drug from the amphetamine family which acts as a monoamine releaser with similar potency to methamphetamine but more selectivity for dopamine and norepinephrine release over serotonin. It is self-administered by mice to a similar extent to related drugs such as 4-fluoroamphetamine and 3-methylamphetamine.
Methoxyketamine or 2-MeO-2-deschloroketamine is a designer drug of the arylcyclohexylamine class first reported in 1963. It is an analog of ketamine in which the chlorine atom has been replaced with a methoxy group. Its synthesis by rearrangement of an amino ketone has been reported. As an arylcyclohexylamine, methoxyketamine most likely functions as an NMDA receptor antagonist. It produces sedative, hallucinogenic, and anesthetic effects, but with a lower potency than ketamine itself.
βk-2C-B (βeta-keto-4-bromo-2,5-dimethoxyphenylamine), also known as bk-2C-B, is a novel psychedelic substance. It is the beta (β) ketone structural analogue of 2C-B, a psychedelic drug of the 2C family. It is used as a recreational drug, usually taken orally. βk-2C-B is a controlled substance in Canada, Germany, Switzerland, and the United Kingdom.
Hydroxybupropion, or 6-hydroxybupropion, is the major active metabolite of the antidepressant and smoking cessation drug bupropion. It is formed from bupropion by the liver enzyme CYP2B6 during first-pass metabolism. With oral bupropion treatment, hydroxybupropion is present in plasma at area under the curve concentrations that are as many as 16 to 20 times greater than those of bupropion itself, demonstrating extensive conversion of bupropion into hydroxybupropion in humans. As such, hydroxybupropion is likely to play a very important role in the effects of oral bupropion, which could accurately be thought of as functioning largely as a prodrug to hydroxybupropion.
Ephenidine is a dissociative anesthetic that has been sold online as a designer drug. It is illegal in some countries as a structural isomer of the banned opioid drug lefetamine, but has been sold in countries where it is not yet banned.
Deschloroketamine is a dissociative anesthetic that has been sold online as a designer drug. It has also been proposed for the treatment of bacterial, fungal, viral or protozoal infections and for immunomodulation at doses of 2 mg per day.
Trifluoromethyldeschloroketamine (TFMDCK) is a designer drug from the arylcyclohexylamine family, which is presumed to have similar properties to ketamine, a dissociative anesthetic drug with hallucinogenic and sedative effects. It has been sold over the internet since around 2016, though genuine samples appear to be rare. The o-trifluoromethyl analogue of hydroxynorketamine has also been researched as an antidepressant.
2-Oxo-PCE is a dissociative anesthetic of the arylcyclohexylamine class that is closely related to deschloroketamine and eticyclidine, and has been sold online as a designer drug.
2-Bromodeschloroketamine is a chemical compound of the arylcyclohexylamine class, which is an analog of the dissociative anesthetic drug ketamine in which the chlorine atom has been replaced with a bromine atom. It is used in scientific research as a comparison or control compound in studies into the metabolism of ketamine and norketamine, and has also been sold online alongside arylcyclohexylamine designer drugs, though it is unclear whether bromoketamine has similar pharmacological activity.
3-Fluorodeschloroketamine is a recreational designer drug related to ketamine. It is from the arylcyclohexylamine family and has dissociative effects. It was made illegal in Finland in August 2019.
2F-NENDCK is a recreational designer drug from the arylcyclohexylamine family, with dissociative effects presumably similar to those of ketamine. Its general effects, dissociative or otherwise, may deviate from other arylcyclohexylamines, however, with one recreational user reporting it felt "very similar to ketamine, but not as deep or introspective".