WC21

WC21 is a small molecule substituted phenylpiperazine that acts as a selective partial agonist of the dopamine D3 receptor. It exhibits approximately 40-fold binding selectivity for the D3 receptor over the D2 receptor subtype, where it also acts as a weak partial agonist. Developed as part of the 'WC series' of dopaminergic ligands, WC21 has been evaluated in preclinical models of Parkinson's disease, specifically the 6-hydroxydopamine (6-OHDA) unilaterally lesioned rat model. In these studies, WC21 demonstrated significant dose-dependent attenuation of L-dopa-induced dyskinesia (LID), showing the highest potency among the series with approximately 90% reduction in abnormal involuntary movement (AIM) scores. Potential side effects observed at higher doses include reduced spontaneous locomotion and ocular ptosis. The research was supported by the Michael J. Fox Foundation and the National Institute on Drug Abuse (NIDA).