BI 1358894 + bupropion

**BI 1358894 + bupropion** is an experimental oral combination of BI 1358894, a selective inhibitor of TRPC4/5 ion channels, and bupropion, a dopamine and noradrenaline reuptake inhibitor. BI 1358894 is under investigation mainly for use in mood and affective disorders, including depression and borderline personality disorder, due to its possible effects on corticolimbic circuits involved in emotional processing and stress regulation[2][4]. Bupropion, approved for major depressive disorder, seasonal affective disorder, and smoking cessation, is also used as augmentation in difficult-to-treat depression and as part of combinations for chronic weight management[1]. The mechanistic rationale for the combination is likely to enhance antidepressant efficacy and modulate affective symptoms through complementary pathways—TRPC4/5 blockade and monoaminergic enhancement, respectively.