UWA-101 is a derivative of phenethylamine invented at the University of Western Australia and investigated as a possible Parkinson’s disease therapy. Its chemical composition is very similar to that of the illicit drug MDMA, with the substitution of the alpha-methyl group with the alpha-cyclopropyl group being the only distinction. MDMA has been found to be successful in the short-term relief of symptoms of Parkinson’s disease in animal studies and documented in unauthorized human self-experiments, especially when used in conjunction with traditional L-DOPA treatment. However the illegal status of MDMA and concerns about its potential for misuse, neurotoxicity and potentially harmful side effects mean that it is unlikely to be tested in this application for medicinal use and alternative analogs have been investigated.
Replacing alpha-methyl with cyclopropyl dramatically reduces affinity for the targets of the noradrenaline transporter and 5-HT2A receptor while maintaining high affinity for the serotonin transporter and significantly increasing affinity for the dopamine transporter (as such, it is one of the few selective SDRIs or inhibitors of serotonin-dopamine reuptake). This shift causes UWA-101 to be deficient in animals in cytotoxicity and MDMA-like behavioral effects, but while maintaining comparable or slightly enhanced anti-Parkinsonian efficacy relative to MDMA. This study was a continuation of the same team’s earlier work that showed that replacing the alpha-methyl MDMA group with larger aromatic ring systems created compounds that lacked psychoactivity and neurotoxicity, but had potent in vitro anti-cancer effects against the lymphoma cells of Burkitt.