Amantadine (DB00915): A Comprehensive Monograph on its Pharmacological Profile, Clinical Utility, and Safety Considerations

Executive Summary

Amantadine is a unique pharmacological agent with a dual, serendipitous history as both an antiviral and an antiparkinsonian drug.[1] Initially developed and approved for the prophylaxis and treatment of Influenza A virus, its clinical utility in this domain has become obsolete due to the emergence of widespread viral resistance.[2] The drug's modern clinical relevance is almost exclusively in the field of neurology, where it serves as a valuable therapy for Parkinson's disease (PD). Its therapeutic effects in the central nervous system (CNS) are attributed to a complex and still incompletely understood mechanism of action, primarily involving the modulation of dopaminergic neurotransmission and non-competitive antagonism of the N-methyl-D-aspartate (NMDA) receptor.[4]

The primary contemporary application of amantadine is in the management of motor complications associated with long-term levodopa therapy in PD. The development and subsequent U.S. Food and Drug Administration (FDA) approval of extended-release (ER) formulations, Gocovri® and Osmolex ER®, have solidified its role in treating levodopa-induced dyskinesia and managing "off" episodes.[6] The drug is also used off-label for various conditions, most notably to accelerate recovery from disorders of consciousness following traumatic brain injury, an application supported by clinical practice guidelines.[2]