Evaluation of the effect of variations in the structure of synthetic cathinones in their psychostimulant properties


Rodríguez i Soler, Miriam  


Drugs of abuse represent a global problem not only at a health level but also at an economic and social extent. There is high availability of drugs and, in some areas, it is rapidly increasing. Internet drug sales are a good example of the speed at which change can occur and raises challenges to existing policy and response models and to drug surveillance. The EU’s Early Warning System for New Psychoactive Substances highlights the importance of being prepared for new challenges when identifying and responding to the emergence of drugs that did not exist until now.
This project has focused on a new family of drugs in the Public Health spotlight due to their rapid growth and appearance in the recreational drug market: synthetic cathinone. They are drugs structurally similar to amphetamine that can have a mechanism of action on dopamine, serotonin, and norepinephrine similar to cocaine, amphetamine, or MDMA.
Structure-activity studies indicate that modifications to the cathinone molecule can influence the in vitro and in vivo potencies, and thus, they may help predict the mechanism of action of a new compound. In order to better understand the mechanism of action of this family, some cathinones have been selected in this project in order to be synthesized and studied pharmacologically. In this way we aim to find the differences in the pharmacological effect of the drug due to variations in its chemical structure, making a comparison between different cathinones. Thus, the synthesized cathinones are pentylone, 4-methyl-pentedrone, and 4-methyl-a-ethylaminopentedrone. In addition, pharmacological studies of N-ethyl-pentylone, previously synthesized in another project, have also been performed. Our study revealed that pentylone, 4-MPD, and 4-MEAP are able to induce potent psychostimulant and rewarding effects in mice. All compounds tested are potent DA uptake inhibitors, with weak effects on SERT. Moreover, high DAT/SERT ratios were obtained, which demonstrates their high abuse potential. Our data also revealed that all the substances are more potent as DAT blockers than cocaine, and the potency as reuptake inhibitors increased with the elongation of the amino substituent from methyl to ethyl.



Berzosa Rodríguez, Xavier
López, Raúl  


IQS SE - Master’s Degree in Pharmaceutical Chemistry