Meclofenoxate Hydrochloride

2‐(Dimethylamino)ethan‐1‐ol (Deanol) is a widely produced chemical used by both industry and consumers in a variety of applications. Meclofenoxate, a stimulant classified on the World Anti‐Doping Agency Prohibited List, metabolizes into deanol and, presumably, its main metabolite deanol‐N‐oxide. Hence, using liquid chromatography–tandem mass spectrometry, a quantitative detection method for deanol‐N‐oxide in urine was developed. Subsequently, the urinary excretion of deanol‐N‐oxide after oral application of 130 mg of deanol was determined in six volunteers, and urine samples of a cohort of 180 male and female athletes from different sports were analyzed. In addition, urinary deanol‐N‐oxide was determined in an exploratory study with one volunteer ingesting 250 mg of meclofenoxate. The developed test method allowed for limits of detection and quantification for deanol‐N‐oxide at 0.05 and 0.15 μg/mL, respectively. Urinary deanol‐N‐oxide cmax levels were found between 100 and 250 μg/mL 2–5 h post‐administration of 130 mg of deanol. Similarly, urine samples collected after the administration of 250 mg of meclofenoxate exhibited cmax levels of 115 μg/mL. In contrast, deanol‐N‐oxide urine concentrations of pre‐administration specimens and 180 routine doping control urine sample were between 0.3 and 1.3 μg/mL and below limit of quantification and 1.8 μg/mL, respectively. The study suggests that the use of deanol and meclofenoxate results in significantly elevated urinary deanol‐N‐oxide levels. Whether or not monitoring deanol‐N‐oxide in doping controls can support decision‐making processes concerning the detection of meclofenoxate use necessitates further investigations taking into consideration the elimination kinetics of 4‐chlorophenoxyacetic acid, the main metabolite of meclofenoxate, and deanol‐N‐oxide.

The first nootropic prohibited in sport was fonturacetam (4-phenylpiracetam, carphedon) in 1998. Presented here 25 years later is a broad-scale consideration of the history, pharmacology, prevalence, regulations, and doping potential of nootropics viewed through a lens of 50 selected dietary supplements (DS) marketed as "cognitive enhancement," "brain health," "brain boosters," or "nootropics," with a focus on unauthorized ingredients. Nootropic DS have risen to prominence over the last decade often as multicomponent formulations of bioactive ingredients presenting compelling pharmacological questions and potential public health concerns. Many popular nootropics are unauthorized food or DS ingredients according to the European Commission including huperzine A, yohimbine, and dimethylaminoethanol; unapproved pharmaceuticals like phenibut or emoxypine (mexidol); previously registered drugs like meclofenoxate or reserpine; EU authorized pharmaceuticals like piracetam or vinpocetine; infamous doping agents like methylhexaneamine or dimethylbutylamine; and other investigational substances and peptides. Several are authorized DS ingredients in the United States resulting in significant global variability as to what qualifies as a legal nootropic. Prohibited stimulants or ß2-agonists commonly used in "pre-workout," "weight loss," or "thermogenic" DS such as octodrine, hordenine, or higenamine are often stacked with nootropic substances. While stimulants and ß2-agonists are defined as doping agents by the World Anti-Doping Agency (WADA), many nootropics are not, although some may qualify as non-approved substances or related substances under catch-all language in the WADA Prohibited List. Synergistic combinations, excessive dosing, or recently researched pharmacology may justify listing certain nootropics as doping agents or warrant additional attention in future regulations.