4,4'-Dimethylaminorex (4,4'-DMAR) has emerged as a notable addition to the realm of novel psychoactive substances (NPS), first appearing on the illicit drug market in 2012. This was associated with 31 tragic deaths across Europe between 2012 and 2013. The compound exists in two racemic mixtures: (±) cis and (±) trans. Analytical studies have identified the (±) cis racemate as the most prevalent form on the market.
What makes (±) cis-4,4'-DMAR particularly intriguing is its triple role as a monoamine-releasing agent. It exhibits equal potency at the dopamine and norepinephrine transporters and even greater potency at the serotonin transporter when compared to d-amphetamine and aminorex. This potent profile not only highlights its potential for abuse but also raises significant concerns. The combination of its chemical properties and the consequence of its misuse makes (±) cis-4,4'-DMAR a substance of considerable interest and concern in equine anti-doping analysis.
In order to identify markers for the abuse of (±) cis-4,4'-DMAR in horses, a single 5 mg dose of (±) cis-4,4'-DMAR was administered to a Standardbred mare. Blood plasma samples were collected up to 24 hours post-dose, and urine samples were collected up to 72 hours post-dose. These samples were extracted at a pH of 12 and analyzed using HPLC-MS-MS. The parent compound, (±) cis-4,4'-DMAR, was detected in blood plasma up to 24 hours after administration and in urine up to 72 hours post-dose. Further analysis of urine samples, both before and after enzyme hydrolysis, indicated that (±) cis-4,4'-DMAR is excreted in urine in its unconjugated form.
The analytical methodology, as well as the comprehensive results of this study, will be described and discussed. This study aims to provide a deeper understanding of the best markers of (±) cis-4,4'-DMAR administration in horses, which is crucial for the development of reliable anti-doping measures in equine sports.