Anticholinergics are the earliest class of pharmaceuticals used for the management of PD. Naturally occurring anticholinergics, such as the belladonna alkaloids, have been used for centuries to treat a variety of ailments. Since the mid-1900s and until the modern development of dopaminergic agents, anticholinergics were a major component of therapy for PD (72). In the 1940s, synthetic anticholinergics were introduced with trihexyphenidyl (Artane®) and similar agents, replacing impure herbal preparations of belladonna alkaloids in the treatment of PD. Eventually, a wide variety of anticholinergics, each with varying receptor specificities, blood-brain barrier penetration, and side effect profiles, became available. Historically and by physician's preference, certain medications have gained popularity or notoriety for particular use in treating PD (73). This has varied throughout the decades. For instance, benzhexol was used as an antiparkinsonian medication in 1972 (73), but is not in common use today.
With recent developments in PD therapy, anticholinergics have been relegated to a distinctly less prominent role. In particular, levodopa and dopamine agonists have largely replaced anticholinergics. Contemporary reviews and investigations continue to support anticholinergic use in certain clinical situations, such as PDassociated tremor or dystonia. Side effects have always been a prominent concern with anticholinergics, particularly in susceptible individuals such as the elderly. As such, careful risk-benefit assessment in anticholinergic use remains a prudent routine practice in PD patients.
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