Trihexyphenidyl is an oral anticholinergic agent used predominantly in the symptomatic therapy of Parkinson’s disease and movement disorders. Trihexyphenidyl has not been associated with serum enzyme elevations during treatment, but has been implicated in rare cases of acute liver injury.
Trihexyphenidyl is an anticholinergic agent that blocks the central cholinergic receptors helping to balance cholinergic transmission in the basal ganglia. Trihexyphenidyl may also block dopamine reuptake and storage in central sites thus increasing dopaminergic activity. The exact mechanism(s) by which the anticholinergic agents are beneficial for symptoms of Parkinson’s disease is unknown. They are used largely in early Parkinsonism and as adjunctive therapy with levodopa or more potent anti-Parkinson’s disease agents. Trihexyphenidyl was approved for use in the United States in 1949 and has been in use since. Current indications include therapy of symptomatic Parkinson’s disease as well as spastic disorders and extrapyramidal disorders due to medications. Trihexyphenidyl is available in tablets of 2 and 5 mg and as an elixir of 2 mg/5 mL in generic forms and formerly under the brand name Artane. The recommended dose is 2 to 5 mg three times daily. Common side effects are due to its anticholinergic activity and include nervousness, confusion, drowsiness, tachycardia, blurred vision, constipation, dry mouth, nausea and urinary retention.
Trihexyphenidyl has not been reported to cause serum aminotransferase elevations, but it has not been evaluated for effects on serum enzyme levels in a prospective manner. Trihexyphenidyl was cited as the cause of two cases of acute liver injury resulting in death in the Japanese literature, but few details were given and there have been no other reports of such injury in the literature in the subsequent 40 years. Thus, trihexyphenidyl must be a very rare cause of liver injury if it occurs at all.
Mechanism of Injury
The metabolism of trihexyphenidyl has not been well defined; it appears to be metabolized in the liver to a small extent.
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