The occurrence of putative cognitive enhancing research peptides in seized pharmaceutical preparations: An incentive for controlling agencies to prepare for future encounters of the kind

Abstract

At the end of 2017 and 2018 two different unknown suspicious preparations were encountered and were subjected to a plethora of different analyses in order to identify, if present, any bioactive compound. It turned out that these samples contained the assumedly cognitive enhancing research peptides Selank and Semax, which, to our knowledge, have not completed any clinical trials. Moreover, an online search, excluding the dark web, demonstrated that these kinds of nootropic research peptides are freely available either as lyophilized powder for injection purposes or are present in nasal sprays. It stands to reason that controlling laboratories need to anticipate the uprising of these types of potentially dangerous molecules and must therefore be able to correctly identify these compounds. Therefore, these findings served as an incentive to develop a novel combined liquid chromatography tandem mass spectroscopy (LC–MS/MS) methodology, applicable to both hydrophilic or more hydrophobic peptides, which was utilized to analyze a total of 10 putative cognitive enhancing polypeptides, with variable biochemical characteristics, that are currently being sold online. The screening rationale, complying to the recommendation paper of the General European Official Medicines Control Laboratory (OMCL) network on the interpretation of screening results for unknown peptides by mass spectrometry, was also validated in different matrices as required by ISO 17025.

The occurrence of non‐anatomical therapeutic chemical‐international nonproprietary name molecules in suspected illegal or illegally traded health products in Europe: A retrospective and prospective study

“…What is more interesting are the new categories, namely, the research peptides and SARMs. Of course, these products have already been the subject of different scientific publications, 18,19,24,25 but this study shows that they are increasing in popularity and are possibly a greater threat to public health than previously assumed. Research peptides, often offered as lyophilisate powder for injection, are sold on the internet as research products that, depending on the type and activity of the peptide present in the product, can be used as a medicine or a doping agent.…”

“…Non‐ATC‐INN drugs are understood as APIs that are not in the ATC‐INN database and therefore not recognised for use as medicines. These can be analogues of registered medicines, including the numerous analogues of sildenafil described in the literature, 15,16 some of which were discarded during drug discovery studies due to their side effects/disadvantageous benefit–risk ratio, 16 or molecules that are still under clinical investigation or that failed clinical trials 17–21 . Needless to say, the use of unapproved medicines, for which no or very little toxicological or clinical data is available, potentially represents a high health risk for the patient or consumer.…”

“…These can be analogues of registered medicines, including the numerous analogues of sildenafil described in the literature, 15,16 some of which were discarded during drug discovery studies due to their side effects/disadvantageous benefit-risk ratio, 16 or molecules that are still under clinical investigation or that failed clinical trials. [17][18][19][20][21] Needless to say, the use of unapproved medicines, for which no or very little toxicological or clinical data is available, potentially represents a high health risk for the patient or consumer. Furthermore, when using dietary supplements, herbal medicines, cosmetics and so forth, the consumer is very often not aware that they are taking a medicine, and especially not a non-approved medicine.…”

Unauthorized ingredients in “nootropic” dietary supplements: A review of the history, pharmacology, prevalence, international regulations, and potential as doping agents

“…A number of experimental peptides designed for cognitive enhancement including Pinealon, Selank, Semax, peptide P21 (also marked as P‐21, P021, or CDKN1A), delta sleep‐inducing peptide (DSIP), and peptide PE‐22‐28 were noted. Other examples of new nootropic substances are Ampalex (CX‐516) and IDRA‐21 (benzothiadiazine derivative) along with ampakines with positive allosteric modulator activity against the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor 176–178 . These substances deserve more scrutiny and analysis in the future, as they are now freely available in the marketplace for consumers or athletes to use.…”