Diphenidine (1,2-DEP, DPD, DND) is a

dissociative Dissociatives, colloquially dissos, are a subclass of hallucinogens which distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of ...

anesthetic An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...

that has been sold as a

designer drug A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. D ...

. 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 Phencyclidine or phenylcyclohexyl piperidine (PCP), also known as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted percept ...

in 1956. Shortly after the 2013 UK ban on

arylcyclohexylamine Arylcyclohexylamines, also known as arylcyclohexamines or arylcyclohexanamines, are a chemical class of pharmaceutical, designer, and experimental drugs. History Phencyclidine (PCP) is believed to be the first arylcyclohexylamine with recog ...

s, diphenidine and the related compound

methoxphenidine Methoxphenidine (methoxydiphenidine, 2-MeO-Diphenidine, MXP) 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 ...

became available on the

grey market A grey market or dark market (sometimes confused with the similar term " parallel market") is the trade of a commodity through distribution channels that are not authorized by the original manufacturer or trade mark proprietor. Grey market pr ...

. 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 The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA and ...

. In dogs diphenidine exhibits greater antitussive potency than codeine phosphate. Electrophysiological analysis demonstrates that the amplitude of NMDA-mediated fEPSPs are reduced by diphenidine and ketamine to a similar extent, with diphenidine displaying a slower onset of antagonism. The two enantiomers of diphenidine differ greatly in their ability to block the NMDA receptor, with the more potent (S)-enantiomer possessing affinity forty times higher than the (R)-enantiomer. Since diphenidine's introduction in 2013 vendors have stated the drug "acts on dopamine transport" yet no data concerning the action of diphenidine on the

dopamine transporter The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dop ...

was published until 2016. Diphenidine's highest affinity is for the NMDA receptor, but it does display submicromolar affinity for the σ₁ receptor, σ₂ receptor and

. Since 2014 there have been several published reports of diphenidine being sold in combination with other research chemicals, particularly synthetic cannabinoids and stimulants in Japanese herbal incense blends. The first reported seizure concerned a Japanese product called "fragrance powder" containing diphenidine and

benzylpiperazine Benzylpiperazine (BZP) is a recreational drug with euphoriant and stimulant properties. The effects produced by BZP are comparable to those produced by amphetamine. Adverse effects have been reported following its use including acute psychosis ...

. A herbal incense sold in the

Shizuoka Prefecture is a prefecture of Japan located in the Chūbu region of Honshu. Shizuoka Prefecture has a population of 3,637,998 and has a geographic area of . Shizuoka Prefecture borders Kanagawa Prefecture to the east, Yamanashi Prefecture to the northea ...

under the name "Aladdin Edition" was found to contain diphenidine and

5F-AB-PINACA 5F-AB-PINACA is an indazole-based synthetic cannabinoid that is derived from a series of compounds originally developed by Pfizer in 2009 as an analgesic medication, and has been sold online as a designer drug. 5F-AB-PINACA has been reported t ...

at concentrations of 289 mg/g and 55.5 mg/g, respectively. A product called ‘‘Herbal Incense. The Super Lemon’’ containing

AB-CHMINACA AB-CHMINACA is an indazole-based synthetic cannabinoid. It is a potent agonist of the CB1 receptor (''K''i = 0.78 nM) and CB2 receptor (''K''i = 0.45 nM) and fully substitutes for Δ9-THC in rat discrimination st ...

5F-AMB 5F-AMB (also known as 5F-MMB-PINACA and 5F-AMB-PINACA) is an indazole-based synthetic cannabinoid from the indazole-3-carboxamide family, which has been used as an active ingredient in synthetic cannabis products. It was first identified in Japan ...

, and diphenidine was implicated in a fatal poisoning. Most recently diphenidine consumed in conjunction with three substituted cathinones, three

benzodiazepines Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

, and alcohol was implicated in a fatal ingestion of "bath salt" and "liquid aroma" products in Japan. In Canada, MT-45 and its analogues were made Schedule I controlled substances. Possession without legal authority can result in maximum seven years imprisonment. Further,

Health Canada Health Canada (HC; french: Santé Canada, SC)Health Canada is the applied title under the Federal Identity Program; the legal title is Department of Health (). is the department of the Government of Canada responsible for national health poli ...

amended the ''Food and Drug Regulations'' in May, 2016 to classify DND as a restricted drug. Only those with a law enforcement agency, person with an exemption permit or institutions with Minister's authorization may possess the drug.

References

{{Ionotropic glutamate receptor modulators Designer drugs Dissociative drugs NMDA receptor antagonists 1-Piperidinyl compounds Diarylethylamines

See also

References