Rasagiline (DB01367): A Comprehensive Pharmacological and Clinical Monograph

1.0 Introduction: Profile of a Second-Generation MAO-B Inhibitor

1.1 Overview and Therapeutic Context

Rasagiline is a second-generation, selective, and irreversible inhibitor of the enzyme monoamine oxidase type B (MAO-B), which holds a prominent position in the contemporary pharmacotherapeutic armamentarium for Parkinson's disease (PD).[1] It is indicated for the symptomatic management of idiopathic PD, serving a dual role as an initial monotherapy in the early stages of the disease and as an adjunctive therapy to levodopa in patients with more advanced disease experiencing motor fluctuations.[3]

Developed as a successor to the first-generation MAO-B inhibitor, selegiline, Rasagiline was engineered to retain the therapeutic benefits of MAO-B inhibition while improving upon the pharmacological profile of its predecessor. Key differentiating features that have defined its clinical utility include a convenient once-daily dosing regimen and, most notably, a metabolic pathway that does not produce amphetamine derivatives, thereby avoiding the associated sympathomimetic side effects.[1] As a small molecule therapeutic agent, Rasagiline represents a significant milestone in the targeted management of dopaminergic dysfunction in PD.[3]

1.2 Rationale for Development

The development of Rasagiline was driven by a clear and unmet clinical need in the management of Parkinson's disease. The cornerstone of PD therapy, levodopa, while highly effective, is associated with the emergence of long-term motor complications, including the "wearing-off" phenomenon and dyskinesias, in a majority of patients.[7] This created a demand for therapeutic strategies that could either delay the need for levodopa initiation or manage its complications once they arise.