Chemistry:Diphenidine

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Short description: Dissociative anesthetic designer drug
Diphenidine
Diphenidine.svg
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC19H23N
Molar mass265.400 g·mol−1
3D model (JSmol)
Melting point210 °C (410 °F)

Diphenidine (1,2-DEP, DPD, DND) is a dissociative anesthetic that has been sold as a designer drug.[1][2][3] 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.[1] Shortly after the 2013 UK ban on arylcyclohexylamines, diphenidine and the related compound methoxphenidine became available on the grey market.[1] Anecdotal reports describe high doses of diphenidine producing "bizarre somatosensory phenomena and transient anterograde amnesia."[1] Diphenidine and related diarylethylamines have been studied in vitro as treatments for neurotoxic injury and are antagonists of the NMDA receptor.[4][5][6][7][8] In dogs diphenidine exhibits greater antitussive potency than codeine phosphate.[9][10]

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.[6] 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.[5] 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 was published until 2016.[1] Diphenidine's highest affinity is for the NMDA receptor, but it does display submicromolar affinity for the σ1 receptor, σ2 receptor and dopamine transporter.[11][12]

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.[13][14][15] The first reported seizure concerned a Japanese product called "fragrance powder" containing diphenidine and benzylpiperazine.[16] A herbal incense sold in the Shizuoka Prefecture under the name "Aladdin Spacial [sic] Edition" was found to contain diphenidine and 5F-AB-PINACA at concentrations of 289 mg/g and 55.5 mg/g, respectively.[13] A product called Herbal Incense. The Super Lemon containing AB-CHMINACA, 5F-AMB, and diphenidine was implicated in a fatal poisoning.[14] Most recently diphenidine consumed in conjunction with three substituted cathinones, three benzodiazepines, and alcohol was implicated in a fatal ingestion of "bath salt" and "liquid aroma" products in Japan.[17]

In Canada, MT-45 and its analogues were made Schedule I controlled substances, which includes DPD in its structural group.[18] Possession without legal authority can result in maximum seven years imprisonment. Further, Health Canada amended the Food and Drug Regulations in May, 2016 to classify explicitly DPD 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.

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 "From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs". Drug Testing and Analysis 6 (7–8): 614–632. July–August 2014. doi:10.1002/dta.1620. PMID 24678061. 
  2. ↑ "Diphenidine, a new psychoactive substance: metabolic fate elucidated with rat urine and human liver preparations and detectability in urine using GC-MS, LC-MSn , and LC-HR-MSn". Drug Testing and Analysis 8 (10): 1005–1014. October 2016. doi:10.1002/dta.1946. PMID 26811026. 
  3. ↑ "Intoxications by the dissociative new psychoactive substances diphenidine and methoxphenidine". Clinical Toxicology 53 (5): 446–453. June 2015. doi:10.3109/15563650.2015.1033630. PMID 25881797. 
  4. ↑ Gray NM, Cheng BK, "1,2-diarylethylamines for treatment of neurotoxic injury", EP patent 0346791, issued 6 April 1994
  5. ↑ 5.0 5.1 "NMDA receptor affinities of 1,2-diphenylethylamine and 1-(1,2-diphenylethyl)piperidine enantiomers and of related compounds". Bioorganic & Medicinal Chemistry 17 (9): 3456–3462. May 2009. doi:10.1016/j.bmc.2009.03.025. PMID 19345586. 
  6. ↑ 6.0 6.1 "Preparation and characterization of the 'research chemical' diphenidine, its pyrrolidine analogue, and their 2,2-diphenylethyl isomers". Drug Testing and Analysis 7 (5): 358–367. May 2015. doi:10.1002/dta.1689. PMID 25044512. http://researchonline.ljmu.ac.uk/id/eprint/3408/1/DTA-14-0117.R1.pdf. Retrieved 2019-12-10. 
  7. ↑ "Active NMDA glutamate receptors are expressed by mammalian osteoclasts". The Journal of Physiology 518 (Pt 1): 47–53. July 1999. doi:10.1111/j.1469-7793.1999.0047r.x. PMID 10373688. 
  8. ↑ "Therapeutic potential of excitatory amino acid antagonists: channel blockers and 2,3-benzodiazepines". Trends in Pharmacological Sciences 14 (9): 325–331. September 1993. doi:10.1016/0165-6147(93)90005-5. PMID 7504360. 
  9. ↑ "Piperidino Groups in Antitussive". Journal of Medicinal Chemistry 6 (2): 118–122. March 1963. doi:10.1021/jm00338a007. PMID 14188779. 
  10. ↑ "Are unconventional NMDA receptors involved in slowly adapting type I mechanoreceptor responses?". Neuroscience 133 (3): 763–773. May 2005. doi:10.1016/j.neuroscience.2005.03.018. PMID 15908129. 
  11. ↑ "Pharmacological Investigations of the Dissociative 'Legal Highs' Diphenidine, Methoxphenidine and Analogues". PLOS ONE 11 (6): e0157021. 17 June 2016. doi:10.1371/journal.pone.0157021. PMID 27314670. Bibcode: 2016PLoSO..1157021W. 
  12. ↑ "Mechanistic Insights into the Stimulant Properties of Novel Psychoactive Substances (NPS) and Their Discrimination by the Dopamine Transporter-In Silico and In Vitro Exploration of Dissociative Diarylethylamines". Brain Sciences 8 (4): 63. April 2018. doi:10.3390/brainsci8040063. PMID 29642450. 
  13. ↑ 13.0 13.1 "A large amount of new designer drug diphenidine coexisting with a synthetic cannabinoid 5-fluoro-AB-PINACA found in a dubious herbal product". Forensic Toxicology 32 (2): 331–337. August 2014. doi:10.1007/s11419-014-0240-y. 
  14. ↑ 14.0 14.1 "Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection of the drugs in unchanged forms". Forensic Toxicology 33 (1): 45–53. January 2015. doi:10.1007/s11419-014-0245-6. 
  15. ↑ "A synthetic cannabinoid FDU-NNEI, two 2H-indazole isomers of synthetic cannabinoids AB-CHMINACA and NNEI indazole analog (MN-18), a phenethylamine derivative N-OH-EDMA, and a cathinone derivative dimethoxy-α-PHP, newly identified in illegal products". Forensic Toxicology 33 (2): 244–259. July 2015. doi:10.1007/s11419-015-0268-7. PMID 26257833. 
  16. ↑ "Diphenidine and its metabolites in blood and urine analyzed by MALDI-Q-TOF mass spectrometry". Forensic Toxicology 33 (2): 402–408. July 2015. doi:10.1007/s11419-015-0273-x. 
  17. ↑ "A fatal case of poisoning related to new cathinone designer drugs, 4-methoxy PV8, PV9, and 4-methoxy PV9, and a dissociative agent, diphenidine". Legal Medicine 17 (5): 421–426. September 2015. doi:10.1016/j.legalmed.2015.06.005. PMID 26162997. 
  18. ↑ "Regulations Amending the Food and Drug Regulations (Parts G and J — Lefetamine, AH-7921, MT-45 and W-18)". Canada Gazette 150 (11). 1 June 2016. http://www.gazette.gc.ca/rp-pr/p2/2016/2016-06-01/html/sor-dors106-eng.php. Retrieved 2016-11-17. 



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