title: Preparation and characterization of the 'research chemical' diphenidine, its pyrrolidine analogue, and their 2,2-diphenylethyl isomers.
abstract: Substances with the diphenylethylamine nucleus represent a recent addition to the product catalog of dissociative agents sold as 'research chemicals' on the Internet. Diphenidine, i.e. 1-(1,2-diphenylethyl)piperidine (1,2-DEP), is such an example but detailed analytical data are less abundant. The present study describes the synthesis of diphenidine and its most obvious isomer, 1-(2,2-diphenylethyl)piperidine (2,2-DEP), in order to assess the ability to differentiate between them. Preparation and characterization were also extended to the two corresponding pyrrolidine analogues 1-(1,2-diphenylethyl)- and 1-(2,2-diphenylethyl)pyrrolidine, respectively. Analytical characterizations included high-resolution electrospray mass spectrometry (HR-ESI-MS), liquid chromatography ESI-MS/MS, gas chromatography ion trap electron and chemical ionization MS, nuclear magnetic resonance spectroscopy (NMR) and infrared spectroscopy. Differentiation between the two isomeric pairs was possible under GC-(EI/CI)-MS conditions and included the formation of distinct iminium ions, such as m/z 174 for 1,2-DEP and m/z 98 for 2,2-DEP, respectively. The pyrrolidine counterparts demonstrated similar phenomena including the expected mass difference of 14 Da due to the lack of one methylene unit in the ring. Two samples obtained from an Internet vendor provided confirmation that diphenidine was present in both samples, concurring with the product label. Finally, it was confirmed that diphenidine (30 μM) reduced N-methyl-D-aspartate-mediated field excitatory postsynaptic potentials (NMDA-fEPSPs) to a similar extent to that of ketamine (30 μM) when using rat hippocampal slices. The appearance of 1,2- diphenylethylamines appears to reflect the exploration of alternatives to arylcyclohexylamine-type substances, such as methoxetamine, PCP and PCPy-based analogues that also show NMDA receptor activity as demonstrated here for diphenidine.
authors.affiliation: Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, 19104, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Wallach
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. James Hospital, Dublin 8, Ireland.
authors.forename: Pierce V
authors.initials: PV
authors.lastname: Kavanagh
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. James Hospital, Dublin 8, Ireland.|Department of Life and Physical Sciences, School of Science, Athlone Institute of Technology, Dublin Road, Athlone, Co., Westmeath, Ireland.
authors.forename: Gavin
authors.initials: G
authors.lastname: McLaughlin
authors.affiliation: Department of Life and Physical Sciences, School of Science, Athlone Institute of Technology, Dublin Road, Athlone, Co., Westmeath, Ireland.
authors.forename: Noreen
authors.initials: N
authors.lastname: Morris
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. James Hospital, Dublin 8, Ireland.
authors.forename: John D
authors.initials: JD
authors.lastname: Power
authors.affiliation: ROAR Forensics, Malvern Hills Science Park, Geraldine Road, WR14 3SZ, UK.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Elliott
authors.affiliation: Department of Physiology and Pharmacology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK.
authors.forename: Marion S
authors.initials: MS
authors.lastname: Mercier
authors.affiliation: Department of Physiology and Pharmacology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK.
authors.forename: David
authors.initials: D
authors.lastname: Lodge
authors.affiliation: Department of Anthropology, The New School for Social Research, 66 West 12th Street, NY, 10011, New York, USA.
authors.forename: Hamilton
authors.initials: H
authors.lastname: Morris
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Dempster
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Brandt
mesh_terms: D000818:Animals; D002623:Chemistry Techniques, Analytical / Q000379:methods*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D007536:Isomerism; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011759:Pyrrolidines / Q000737:chemistry*; D051381:Rats
chemical_list: D010880:Piperidines; D011759:Pyrrolidines; D007649:Ketamine; C000599677:diphenidine
keywords: Internet; NMDA receptor; PCP; arylcyclohexylamines; diarylethylamines; diphenidine; isomers; psychoactive; ‘research chemicals’