 |
Related Articles |
Synthetic Cathinone Analogs Structurally Related to the Central Stimulant Methylphenidate as Dopamine Reuptake Inhibitors.
ACS Chem Neurosci. 2019 Aug 01;:
Authors: Yadav-Samudrala BJ, Eltit JM, Glennon RA
Abstract
Synthetic cathinones are, primarily, stimulant drugs of abuse that act at monoamine transporters (e.g. the dopamine transporter or DAT) as releasing agents or as reuptake inhibitors. In the past few years the emergence of >150 new synthetic cathinones has attracted considerable attention from medical and law enforcement communities. threo-Methylphenidate (tMP), used clinically for the treatment of ADHD and narcolepsy, is also a DAT reuptake inhibitor. tMP is somewhat structurally similar to abused cathinone stimulants and the structure-activity relationships (SAR) of tMP have been well defined. Hence, available tMP literature might assist in understanding the SAR of synthetic cathinones, about which less is known. In the present study we synthesized and examined eight 2-benzoylpiperidine analogs (4, 6-12) to determine if tMP SAR might be applicable to cathinone SAR. The benzoylpiperidine analogs were evaluated in a competition assay using live-cell imaging against APP+ in HEK293 cells stably expressing hDAT and in cells co-expressing DAT and voltage-gated Ca2+ channels. All compounds were found to be DAT reuptake inhibitors and a significant correlation was obtained between the potency of the benzoylpiperidines and tMP binding data (r = 0.91) suggesting that the SAR of tMP analogs might be directly applicable to certain synthetic cathinones as DAT reuptake inhibitors.
PMID: 31369229 [PubMed – as supplied by publisher]
via https://www.ncbi.nlm.nih.gov/pubmed/31369229?dopt=Abstract