When Dopamine Never Sleeps: Chronopharmacologic Insights into Continuous 24-Hour Infusion Therapy

Background: Dopamine plays a pivotal role not only in motor control but also in the regulation of circadian rhythms and sleep–wake architecture. Continuous dopaminergic stimulation (CDS), achieved through 24-hour levodopa/carbidopa infusion, provides stable dopaminergic tone in advanced Parkinson’s disease (PD). While this strategy improves motor fluctuations, its influence on diurnal dopamine physiology and circadian homeostasis remains poorly understood. Objective: This review critically examines how 24-hour dopaminergic infusion may interact with endogenous dopamine rhythms, clock gene expression, and sleep–REM physiology, areas largely underexplored in current literature. Methods: A comprehensive PubMed search was conducted through February 2025 using terms related to “dopamine,” “circadian rhythm,” “continuous dopaminergic stimulation,” and “sleep architecture.” Animal and human studies addressing dopaminergic circadian modulation or infusion therapies were synthesized. Results: Evidence suggests that CDS may flatten physiological dopamine oscillations, induce receptor desensitization, and influence REM/NREM regulation and peripheral clock gene activity. Preliminary clinical findings indicate improved subjective sleep quality but uncertain effects on circadian entrainment. Conclusion: Continuous 24-hour dopaminergic infusion represents a major therapeutic advance in PD. However, its chronopharmacologic effects on circadian signaling and sleep structure warrant systematic investigation through polysomnography and molecular chronobiology to optimize both motor and non-motor outcomes.