Analysis of six “neuro-enhancing” phenidate analogs

Six collected phenidates, i.e. 4-methylmethylphenidate, 3,4-dichloromethylphenidate, ethylphenidate, 3,4-dichloroethylphenidate, ethylnaphthidate and N-benzyl-ethylphenidate were fully characterized by means of X-ray, NMR, GC-MS, ESI-MS2, ATR-FT-IR and GC solid-state IR analysis. Crystallography revealed the exclusive presence of the threo-configuration. Steric crowding induced by N-benzyl substitution at the piperidine moiety prompted an adoption of an unexpected axial positioning of substituents on the piperidine moiety in the crystal state as opposed to the exclusive equatorial positioning encountered in N-unsubstituted phenidate analogs. Gas phase computations of the relative lowest energy conformers confirm that the axial positioning appears to be favored over the equatorial positioning, however in solution equatorial positioning is predominant according to NOE experiments. All samples, mainly originating from China, had a good to very good degree of purity indicative of their professional chemical synthesis. Routine analysis of these drugs by GC-MS revealed thermal decomposition of phenidate analogs in the injection port and/or on column to 2-aryl-ethyl-acetates and 2,3,4,5-tetrahydropyridines. The decomposition pathway was suggested to proceed via a 6-membered transition state which was supported by DFT-computations. Fragmentation pathways of decomposition products as well as the corresponding EI mass spectra are provided. The thermal instability might thus render smoking or “vaping” of these drugs a less effective route of administration. The analytical fingerprints of six structurally diverse phenidate analogs provide a helpful reference to forensic chemists in charge of identifying new psychoactive substances

Environmental enrichment has no effect on the development of dopaminergic and GABAergic fibers during methylphenidate treatment of early traumatized gerbils

It is widely believed, that environmental factors play a crucial role in the etiology and outcome of psychiatric diseases such as Attention-Deficit/Hyperactivity Disorder (ADHD). A former study from our laboratory has shown that both methylphenidate (MP) and handling have a positive effect on the dopaminergic fiber density in the prefrontal cortex (PFC) of early traumatized gerbils (Meriones unguiculatus). The current study was performed to investigate if enriched environment during MP application has an additional influence on the dopaminergic and GABAergic fiber densities in the PFC and amygdala in this animal model