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.
Phencyclidine or phenylcyclohexyl piperidine (PCP), also known in its use as a street drug as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted perceptions of sounds, and violent behavior. As a recreational drug, it is typically smoked, but may be taken by mouth, snorted, or injected. It may also be mixed with cannabis or tobacco.
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. Dizocilpine is also associated with a number of negative side effects, including cognitive disruption and psychotic-spectrum reactions. It inhibits the induction of long term potentiation and has been found to impair the acquisition of difficult, but not easy, learning tasks in rats and primates. Because of these effects of dizocilpine, the NMDA receptor pore blocker ketamine is used instead as a dissociative anesthetic in human medical procedures. While ketamine may also trigger temporary psychosis in certain individuals, its short half-life and lower potency make it a much safer clinical option. However, dizocilpine is the most frequently used uncompetitive NMDA receptor antagonist in animal models to mimic psychosis for experimental purposes.
Memantine, sold under the brand name Axura among others, is a medication used to slow the progression of moderate-to-severe Alzheimer's disease. It is taken by mouth.
Tiletamine is a dissociative anesthetic and pharmacologically classified as an NMDA receptor antagonist. It is related chemically to ketamine. Tiletamine hydrochloride exists as odorless white crystals.
NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the N-Methyl-D-aspartate receptor (NMDAR). They are commonly used as anesthetics for humans and animals; the state of anesthesia they induce is referred to as dissociative anesthesia.
Tenocyclidine (TCP) is a dissociative anesthetic with psychostimulant effects. It was discovered by a team at Parke-Davis in the late 1950s. It is similar in effects to phencyclidine (PCP) but is considerably more potent. TCP has slightly different binding properties to PCP, with more affinity for the NMDA receptors, but less affinity for the sigma receptors. Because of its high affinity for the PCP site of the NMDA receptor complex, the 3H radiolabelled form of TCP is widely used in research into NMDA receptors.
Arylcyclohexylamines, also known as arylcyclohexamines or arylcyclohexanamines, are a chemical class of pharmaceutical, designer, and experimental drugs.
Methoxetamine, abbreviated as MXE, is a dissociative hallucinogen that has been sold as a designer drug. It differs from many dissociatives such as ketamine and phencyclidine (PCP) that were developed as pharmaceutical drugs for use as general anesthetics in that it was designed specifically to increase the antidepressant effects of ketamine.
MT-45 (IC-6) is an opioid analgesic drug invented in the 1970s by Dainippon Pharmaceutical Co. It is chemically a 1-substituted-4-(1,2-diphenylethyl) piperazine derivative, which is structurally unrelated to most other opioid drugs. Racemic MT-45 has around 80% the potency of morphine, with almost all opioid activity residing in the (S) enantiomer. It has been used as a lead compound from which a large family of potent opioid drugs have been developed, including full agonists, partial agonists, and antagonists at the three main opioid receptor subtypes. Fluorinated derivatives of MT-45 such as 2F-MT-45 are significantly more potent as μ-opioid receptor agonists, and one of its main metabolites 1,2-diphenylethylpiperazine also blocks NMDA receptors.
25D-NBOMe is a derivative of the phenethylamine derived hallucinogen 2C-D. It acts in a similar manner to related compounds such as 25I-NBOMe, which is a potent agonist at the 5-HT2A receptor. 25D-NBOMe has been sold as a street drug since 2010 and produces similar effects in humans to related compounds such as 25I-NBOMe and 25C-NBOMe. It was banned as a Temporary Class Drug in the UK on 10 June 2013 after concerns about its recreational use.
Diphenidine is a dissociative anesthetic that has been sold as a designer drug. The synthesis of diphenidine was first reported in 1924, and employed a Bruylants reaction analogous to the one that would later be used to discover phencyclidine in 1956. Shortly after the 2013 UK ban on arylcyclohexylamines, diphenidine and the related compound methoxphenidine became available on the grey market. Anecdotal reports describe high doses of diphenidine producing "bizarre somatosensory phenomena and transient anterograde amnesia." Diphenidine and related diarylethylamines have been studied in vitro as treatments for neurotoxic injury and are antagonists of the NMDA receptor. In dogs diphenidine exhibits greater antitussive potency than codeine phosphate.
Methoxphenidine is a dissociative of the diarylethylamine class that has been sold online as a designer drug. Methoxphenidine was first reported in a 1989 patent where it was tested as a treatment for neurotoxic injury. Shortly after the 2013 UK ban on arylcyclohexylamines methoxphenidine and the related compound diphenidine became available on the gray market, where it has been encountered as a powder and in tablet form. Though diphenidine possesses higher affinity for the NMDA receptor, anecdotal reports suggest methoxphenidine has greater oral potency. Of the three isomeric anisyl-substituents methoxphenidine has affinity for the NMDA receptor that is higher than 4-MeO-diphenidine but lower than 3-MeO-diphenidine, a structure–activity relationship shared by the arylcyclohexylamines.
25N-NBOMe is a derivative of the hallucinogen 2C-N. The pharmacological properties of 25N-NBOMe have not been described in the scientific literature, but it is believed to act in a similar manner to related compounds such as 25I-NBOMe and 25C-NBOMe, which are potent agonists at the 5HT2A receptor. 25N-NBOMe has been sold as a street drug and has only been described in the literature in terms of identification by forensic analysis.
25E-NBOMe is a derivative of the phenethylamine 2C-E. It acts in a similar manner to related compounds such as 25I-NBOMe, which are potent agonists at the 5-HT2A receptor. 25E-NBOMe has been sold as a drug and produces similar effects in humans to related compounds such as 25I-NBOMe and 25C-NBOMe.
'MDMB-CHMICAa' is an indole-based synthetic cannabinoid that is a potent agonist of the CB1 receptor and has been sold online as a designer drug. While MDMB-CHMICA was initially sold under the name "MMB-CHMINACA", the compound corresponding to this code name (i.e. the isopropyl instead of t-butyl analogue of MDMB-CHMINACA) has been identified on the designer drug market in 2015 as AMB-CHMINACA.
25iP-NBOMe is a derivative of the phenethylamine hallucinogen 2C-iP, which acts as a highly potent agonist for the human 5-HT2A receptor.
Dextromethorphan/bupropion (DXM/BUP), sold under the brand name Auvelity, is a combination medication for the treatment of major depressive disorder (MDD). Its active components are dextromethorphan (DXM) and bupropion. Patients who stayed on the medication had an average of 11% greater reduction in depressive symptoms than placebo in an FDA approval trial. It is taken as a tablet by mouth.
The 25-NB (25x-NBx) series, sometimes alternatively referred to as the NBOMe compounds, is a family of serotonergic psychedelics. They are substituted phenethylamines and were derived from the 2C family. They act as selective agonists of the serotonin 5-HT2A receptor. The 25-NB family is unique relative to other classes of psychedelics in that they are, generally speaking, extremely potent and relatively selective for the 5-HT2A receptor. Use of NBOMe series drugs has caused many deaths and hospitalisations since the drugs popularisation in the 2010s. This is primarily due to their high potency, unpredictable pharmacokinetics, and sellers passing off the compounds in the series as LSD.
25E-NBOH is a derivative of the phenethylamine derived hallucinogen 2C-E. It was first developed by Martin Hansen at the University of Copenhagen in 2010 as a brain imaging agent, but has subsequently been sold as a designer drug, first being identified in Brazil in 2018 on seized blotter paper, as well as in Slovenia and France. It acts as a potent serotonin receptor agonist with similar affinity to better-known compounds such as 25I-NBOMe at 5-HT2A and 5-HT2C receptors.
