Apomorphine: past, present and future in Parkinson's disease and beyond

The year 2025 marks the 180th anniversary of the first documented synthesis of apomorphine, and the first U.S. Food and Drug Administration (FDA) approval of a subcutaneous apomorphine infusion device for advanced Parkinson's disease (SPN-830). This narrative review therefore aims to examine apomorphine clinical journey, celebrating its turbulent yet founding past, analyzing its current challenges in the treatment of Parkinson's disease (PD) and envisioning its promising future, both in neurological disorders and beyond. Enduring misconceptions and the lack of class 1 evidence for supporting the use of continuous subcutaneous apomorphine infusion (CSAI) in PD have long been thought to have prevented its generalized use. The TOLEDO study, which robustly demonstrated a clinically meaningful reduction in off time (as expected based on decades of clinical experience) has now removed this barrier. Challenges to be addressed moving forward include (1) redefining the place of apomorphine in the PD treatment paradigm (from early use to terminal care), (2) reducing access disparities (availability, cost), (3) improving delivery systems and apomorphine formulations, and (4) expanding clinical use both in and outside of neurological disorders, with already tangible results for atypical Parkinsonian syndromes and disorders of consciousness, and promising perspectives in Alzheimer's disease.