Possible pathway to a drug to combat cocaine addiction

2023-09-06 17:45:44

Cocaine use continues to be a severe public health problem. In the United States alone, more than 5 million people reported active cocaine use in 2020, and nearly 25,000 died of a cocaine-related overdose in 2021, according to figures from the Centers for Disease Control and Prevention (CDC). ) from the United States.

Despite the efforts that have been made, there is a great gap in terms of drugs capable of solving cocaine addiction.

Some research suggests that methylphenidate (MPH; Ritalin®), which is a drug for attention deficit hyperactivity disorder, could serve as a cocaine replacement therapy. MPH behaves similarly to cocaine in that it increases dopamine levels in the brain by blocking dopamine reuptake. In addition, clinical studies have shown that the risk of MPH is lower than that of cocaine.

Although animal studies have shown that MPH can reduce cocaine dependence, human studies have given mixed results.

Although several laboratories produced MPH derivatives for testing, chemically inaccessible parts of the molecule remained. Until recently it was difficult to create derivatives of one of MPH’s chemical components: its piperidine ring.

Now, researchers have overcome that hurdle.

Cocaine. (Photo: DEA)

A team including Jonathan D. Dabbs and W. Dean Harman, both from the University of Virginia in Charlottesville, USA, set out to address this shortcoming by taking an organometallic approach.

Using a tungsten-based reagent, the researchers synthesized a library of MPH analogues specifically modified at the piperidine ring with various chemical groups.

And while MPH is a mixture of four isomers (identical molecules with minor structural differences), the new method allowed the researchers to synthesize and purify compounds that consisted predominantly of a single isomer. This could be important in clinical studies, as different isomers of some drugs can have significant implications for therapeutic efficacy or safety.

Whether any of these MPH analogues are effective against cocaine addiction remains to be determined, but the researchers noted that the new protocol could be broadly applicable to pharmaceutical development, given the ubiquity of the piperidine ring in small-molecule drugs.

The study is titled “The Tungsten-Promoted Synthesis of Piperidyl-Modified Erythro-Methylphenidate Derivatives”. And it has been published in the academic journal ACS Central Science. (Source: American Chemical Society)