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Diphenidine

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Diphenidine
Legal status
Legal status
Identifiers
  • (±)-1-(1,2-Diphenylethyl)piperidine
CAS Number
PubChemCID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard(EPA)
Chemical and physical data
FormulaC19H23N
Molar mass265.400g·mol−1
3D model (JSmol)
Melting point210 °C (410 °F)
  • c1ccc(cc1)CC(c2ccccc2)N3CCCCC3
  • InChI=1S/C19H23N/c1-4-10-17(11-5-1)16-19(18-12-6-2-7-13-18)20-14-8-3-9-15-20/h1-2,4-7,10-13,19H,3,8-9,14-16H2
  • Key:JQWJJJYHVHNXJH-UHFFFAOYSA-N

Diphenidine(1,2-DEP,DPD,DND) is adissociativeanestheticthat has been sold as adesigner drug.[2][3][4]The synthesis of diphenidine was first reported in 1924, and employed a Bruylants reaction analogous to the one that would later be used to discoverphencyclidinein 1956.[2]Shortly after the 2013 UK ban onarylcyclohexylamines,diphenidine and the related compoundmethoxphenidinebecame available on thegrey market.[2]Anecdotal reports describe high doses of diphenidine producing "bizarre somatosensory phenomena and transient anterograde amnesia."[2]Diphenidine and related diarylethylamines have been studied in vitro as treatments for neurotoxic injury and are antagonists of theNMDA receptor.[5][6][7][8][9]In dogs diphenidine exhibits greater antitussive potency thancodeine phosphate.[10][11]

Electrophysiologicalanalysis demonstrates that the amplitude of NMDA-mediatedfEPSPsare reduced by diphenidine and ketamine to a similar extent, with diphenidine displaying a slower onset of antagonism.[7]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.[6]Since diphenidine's introduction in 2013 vendors have stated the drug "acts on dopamine transport" yet no data concerning the action of diphenidine on thedopamine transporterwas published until 2016.[2]Diphenidine's highest affinity is for the NMDA receptor, but it does display submicromolar affinity for theσ1receptor,σ2receptoranddopamine transporter.[12][13]

Since 2014 there have been several published reports of diphenidine being sold in combination with other research chemicals, particularly synthetic cannabinoids and stimulants in Japaneseherbal incenseblends.[14][15][16]The first reported seizure concerned a Japanese product called "fragrance powder" containing diphenidine andbenzylpiperazine.[17]Aherbal incensesold in theShizuoka Prefectureunder the name "Aladdin Spacial [sic] Edition "was found to contain diphenidine and5F-AB-PINACAat concentrations of 289 mg/g and 55.5 mg/g, respectively.[14]A product calledHerbal Incense. The Super LemoncontainingAB-CHMINACA,5F-AMB,and diphenidine was implicated in a fatal poisoning.[15]Most recently diphenidine consumed in conjunction with threesubstituted cathinones,threebenzodiazepines,and alcohol was implicated in a fatal ingestion of "bath salt" and "liquid aroma" products in Japan.[18]

In Canada, MT-45 and its analogues were made Schedule I controlled substances, which includes DPD in its structural group.[19]Possession without legal authority can result in maximum seven years imprisonment. Further,Health Canadaamended theFood and Drug Regulationsin 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[edit]

References[edit]

  1. ^Anvisa(2023-07-24)."RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial"[Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese).Diário Oficial da União(published 2023-07-25).Archivedfrom the original on 2023-08-27.Retrieved2023-08-27.
  2. ^abcdeMorris H, Wallach J (July–August 2014). "From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs".Drug Testing and Analysis.6(7–8): 614–632.doi:10.1002/dta.1620.PMID24678061.
  3. ^Wink CS, Michely JA, Jacobsen-Bauer A, Zapp J, Maurer HH (October 2016). "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.doi:10.1002/dta.1946.PMID26811026.
  4. ^Helander A, Beck O, Bäckberg M (June 2015). "Intoxications by the dissociative new psychoactive substances diphenidine and methoxphenidine".Clinical Toxicology.53(5): 446–453.doi:10.3109/15563650.2015.1033630.PMID25881797.S2CID5962038.
  5. ^EP 0346791,Gray NM, Cheng BK, "1,2-diarylethylamines for treatment of neurotoxic injury", issued 6 April 1994, assigned to G.D. Searle, LLC
  6. ^abBerger ML, Schweifer A, Rebernik P, Hammerschmidt F (May 2009). "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.doi:10.1016/j.bmc.2009.03.025.PMID19345586.
  7. ^abWallach J, Kavanagh PV, McLaughlin G, Morris N, Power JD, Elliott SP, et al. (May 2015)."Preparation and characterization of the 'research chemical' diphenidine, its pyrrolidine analogue, and their 2,2-diphenylethyl isomers"(PDF).Drug Testing and Analysis.7(5): 358–367.doi:10.1002/dta.1689.PMID25044512.Archived(PDF)from the original on 2020-03-07.Retrieved2019-12-10.
  8. ^Espinosa L, Itzstein C, Cheynel H, Delmas PD, Chenu C (July 1999)."Active NMDA glutamate receptors are expressed by mammalian osteoclasts".The Journal of Physiology.518(Pt 1): 47–53.doi:10.1111/j.1469-7793.1999.0047r.x.PMC2269403.PMID10373688.
  9. ^Rogawski MA (September 1993). "Therapeutic potential of excitatory amino acid antagonists: channel blockers and 2,3-benzodiazepines".Trends in Pharmacological Sciences.14(9): 325–331.doi:10.1016/0165-6147(93)90005-5.PMID7504360.
  10. ^Kase Y, Yuizono T, Muto M (March 1963). "Piperidino Groups in Antitussive".Journal of Medicinal Chemistry.6(2): 118–122.doi:10.1021/jm00338a007.PMID14188779.
  11. ^Cahusac PM, Senok SS, Hitchcock IS, Genever PG, Baumann KI (May 2005). "Are unconventional NMDA receptors involved in slowly adapting type I mechanoreceptor responses?".Neuroscience.133(3): 763–773.doi:10.1016/j.neuroscience.2005.03.018.PMID15908129.S2CID15610561.
  12. ^Wallach J, Kang H, Colestock T, Morris H, Bortolotto ZA, Collingridge GL, et al. (17 June 2016)."Pharmacological Investigations of the Dissociative 'Legal Highs' Diphenidine, Methoxphenidine and Analogues".PLOS ONE.11(6): e0157021.Bibcode:2016PLoSO..1157021W.doi:10.1371/journal.pone.0157021.PMC4912077.PMID27314670.
  13. ^Sahai MA, Davidson C, Dutta N, Opacka-Juffry J (April 2018)."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.doi:10.3390/brainsci8040063.PMC5924399.PMID29642450.
  14. ^abWurita A, Hasegawa K, Minakata K, Watanabe K, Suzuki O (August 2014). "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.doi:10.1007/s11419-014-0240-y.S2CID25995354.
  15. ^abHasegawa K, Wurita A, Minakata K, Gonmori K, Nozawa H, Yamagishi I, Watanabe K, Suzuki O (January 2015). "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.doi:10.1007/s11419-014-0245-6.S2CID11884184.
  16. ^Uchiyama N, Shimokawa Y, Kikura-Hanajiri R, Demizu Y, Goda Y, Hakamatsuka T (July 2015)."A synthetic cannabinoid FDU-NNEI, two 2H-indazole isomers of synthetic cannabinoids AB-CHMINACA and NNEI indazole analog (MN-18), a phenethylamine derivativeN-OH-EDMA, and a cathinone derivative dimethoxy-α-PHP, newly identified in illegal products ".Forensic Toxicology.33(2): 244–259.doi:10.1007/s11419-015-0268-7.PMC4525202.PMID26257833.
  17. ^Minakata K, Yamagishi I, Nozawa H, Hasegawa K, Wurita A, Gonmori K, Suzuki M, Watanabe K, Suzuki O (July 2015). "Diphenidine and its metabolites in blood and urine analyzed by MALDI-Q-TOF mass spectrometry".Forensic Toxicology.33(2): 402–408.doi:10.1007/s11419-015-0273-x.S2CID44007379.
  18. ^Kudo K, Usumoto Y, Kikura-Hanajiri R, Sameshima N, Tsuji A, Ikeda N (September 2015). "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.doi:10.1016/j.legalmed.2015.06.005.PMID26162997.
  19. ^Arsenault D (1 June 2016)."Regulations Amending the Food and Drug Regulations (Parts G and J — Lefetamine, AH-7921, MT-45 and W-18)".Canada Gazette.150(11).Archivedfrom the original on 2017-12-02.Retrieved2016-11-17.
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