Synthesis and neuropharmacological profile of novel synthetic cathinones. Role of aromatic chlorination of α-PVP derivatives


Lleixà Villar, Esther 


Over the last decade, there has been a marked shift in the illicit drug market with the emergence of a new generation of psychoactive substances. Marketed as "legal drugs" and widely available on the Internet, new psychoactive substances (NSPs) continue to rise rapidly, posing a significant risk to public health. Compared to traditional drugs of abuse, NSPs are cheap, easy to obtain, and their unregulated status in many countries makes them very attractive. Many of these substances often disappear from the market quickly; however, some of them still remain due to their popularity among drug users. Among these substances, synthetic catinones are one of the most prevalent classes of designer drugs that became popular due to the psychoactive effects similar to cocaine, ecstasy, and amphetamines.
The realization of design substitutions in the chemical structure of existing psychoactive drugs lead to the creation of alternative compounds whose chemical, pharmacological and toxicological properties are still unknown. Today, α-PVP is under international control and is considered one of the most persistent NSPs. For this reason, the aim of this project was to synthesize and characterize the pharmacological profile, psychostimulant and rewarding properties of the new synthetic catinones structurally similar to α-PVP and which differ in the position of a chloride group in the aromatic ring.Pharmacological synthesis and characterization of 3-Cl-α-PVP, 4-Cl-α-PVP, and 3,4-Cl-α-PVP was successfully performed. In vivo results revealed that all three compounds can induce an increase in locomotor activity and possess rewarding properties. On the other hand, in vitro results showed that all tested compounds are potent DAT inhibitors but with a low affinity for SERT and their DAT inhibitory potency increases when halogenation is carried out at position 3 and 4 simultaneously. , 3 and finally 4. In addition, the high values ​​of the DAT / SERT ratio obtained show its high potential for abuse.
The present study demonstrated the role of the addition of chlorine to the aromatic ring in the pharmacological profile of the new synthetic catinones providing a first evidence of the potency as well as of their addictive and psychostimulant effects of these compounds.



Berzosa Rodríguez, Xavier
López, Raúl


IQS SE - Master’s Degree in Pharmaceutical Chemistry