Mevidalen is a dopamine D1 receptor subtype-specific positive allosteric modulator (PAM). For a study, researchers sought to determine if mevidalen was safe and effective for treating Lewy body dementia patients’ cognition (LBD). Participants with LBD (N = 344) were randomly allocated (1:1:1:1) to daily dosages of mevidalen (10, 30, or 75 mg) or placebo in the PRESENCE trial. The change in the Cognitive Drug Research Continuity of Attention (CoA) composite score from baseline was the primary outcome measure. The Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-cog13), the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), and the Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change were all used as secondary outcomes (ADCS-CGIC). Several safety precautions were gathered.

The primary and secondary cognitive goals for Mevidalen were not met. Mevidalen improved the MDS-UPDRS total score in a dose-dependent manner (sum of Parts IIII, 10 mg P<0.05, 30 mg P<0.05, 75 mg P<0.01, compared to placebo). When compared to placebo, the 30 mg and 75 mg mevidalen dosages improved ADCS-CGIC scores considerably (minimum or better improvement: 30 mg P<0.01, 75 mg P<0.01; considerable or superior improvement: 30 mg P<0.05, 75 mg P<0.001). The 75 mg dosage caused the highest blood pressure elevations, adverse events, and severe cardiovascular events.

Mevidalen worked through a new mode of action that improved or did not exacerbate non-motor symptoms associated with classic dopaminergic treatment while improving or not worsening motor symptoms associated with LBD.