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yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK547977_"><span class="title" itemprop="name">Trihexyphenidyl</span></h1><p class="fm-aai"><a href="#_NBK547977_pubdet_">Publication Details</a></p></div></div><div class="body-content whole_rhythm" itemprop="text"><div id="Trihexyphenidyl.OVERVIEW"><h2 id="_Trihexyphenidyl_OVERVIEW_">OVERVIEW</h2><div id="Trihexyphenidyl.Introduction"><h3>Introduction</h3><p>Trihexyphenidyl is an oral anticholinergic agent used predominantly in the symptomatic therapy of Parkinson 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.</p></div><div id="Trihexyphenidyl.Background"><h3>Background</h3><p>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 disease is unknown. They are used largely in early Parkinsonism and as adjunctive therapy with levodopa or more potent antiParkinson 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 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.</p></div><div id="Trihexyphenidyl.Hepatotoxicity"><h3>Hepatotoxicity</h3><p>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.</p><p>Likelihood score: E* (unproven but suspected cause of clinically apparent liver injury).</p></div><div id="Trihexyphenidyl.Mechanism_of_Injury"><h3>Mechanism of Injury</h3><p>The metabolism of trihexyphenidyl has not been well defined; it appears to be metabolized in the liver to a small extent.</p><p>Drug Class: <a href="/books/n/livertox/AntiparkinsonAgents/?report=reader">Antiparkinson Agents</a></p><p>Other Drugs in the Subclass, <a href="/books/n/livertox/Anticholinergics/?report=reader">Anticholinergic Agents</a>: <a href="/books/n/livertox/Benztropine/?report=reader">Benztropine</a>, <a href="/books/n/livertox/Biperiden/?report=reader">Biperiden</a></p></div></div><div id="Trihexyphenidyl.PRODUCT_INFORMATION"><h2 id="_Trihexyphenidyl_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><div id="Trihexyphenidyl.BPI" class="box boxed-text-box whole_rhythm hide-overflow"><p>
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<b>REPRESENTATIVE TRADE NAMES</b>
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</p><p>Trihexyphenidyl – Generic, Artane®</p><p>
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<b>DRUG CLASS</b>
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</p><p>Antiparkinson Agents</p><p>
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<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Trihexyphenidyl" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">COMPLETE LABELING</a>
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</p><p>Product labeling at DailyMed, National Library of Medicine, NIH</p></div></div><div id="Trihexyphenidyl.CHEMICAL_FORMULA_AND_STR"><h2 id="_Trihexyphenidyl_CHEMICAL_FORMULA_AND_STR_">CHEMICAL FORMULA AND STRUCTURE</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figTrihexyphenidylT1"><a href="/books/NBK547977/table/Trihexyphenidyl.T1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobTrihexyphenidylT1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="Trihexyphenidyl.T1"><a href="/books/NBK547977/table/Trihexyphenidyl.T1/?report=objectonly" target="object" rid-ob="figobTrihexyphenidylT1">Table</a></h4></div></div></div><div id="Trihexyphenidyl.ANNOTATED_BIBLIOGRAPHY"><h2 id="_Trihexyphenidyl_ANNOTATED_BIBLIOGRAPHY_">ANNOTATED BIBLIOGRAPHY</h2><p>References updated: 20 July 2017</p><ul class="first-line-outdent"><li><div class="bk_ref" id="Trihexyphenidyl.R1">Zimmerman HJ. Antiparkinsonism drugs. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 715-7.<div><i>(Expert review of hepatotoxicity published in 1999; among anticholinergic agents, "only trihexyphenidyl has been incriminated in hepatic injury"; other antiparkinsonism drugs discussed include levodopa, lergotrile [no longer available], pergolide and bromocriptine).</i></div></div></li><li><div class="bk_ref" id="Trihexyphenidyl.R2">Larrey D, Ripault MP. Hepatotoxicity of psychotropic drugs and drugs of abuse. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier Inc, 2013, pp. 443-62.<div><i>(Review of hepatotoxicity of agents acting on the central nervous system).</i></div></div></li><li><div class="bk_ref" id="Trihexyphenidyl.R3">Standaert DG, Roberson ED. Treatment of central nervous system degenerative disorders. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 609-28.<div><i>(Textbook of pharmacology and therapeutics).</i></div></div></li><li><div class="bk_ref" id="Trihexyphenidyl.R4">McDowell F. Symposium on levodopa in Parkinson's disease. Clinical and pharmacological aspects. Clinical laboratory abnormalities. Clin Pharmacol Ther 1971; 12: 335-9.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/4102803" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4102803</span></a>]<div><i>(Retrospective analysis of laboratory abnormalities arising in 974 patients with Parkinson disease treated with levodopa; AST elevations occurred in 9% of 5427 determinations, but were usually mild and transient returning to normal in 1-2 months without dose adjustment; AST levels rose to 1600 U/L in one patient who later died of complications of diabetes).</i></div></div></li><li><div class="bk_ref" id="Trihexyphenidyl.R5">Lambert D, Waters CH. Comparative tolerability of the newer generation antiparkinsonian agents. Drugs Aging 2000; 16: 55-65.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/10733264" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10733264</span></a>]<div><i>(Review of mechanism of action, tolerability and safety of selegiline, pramipexole, ropinirole, tolcapone and entacapone in Parkinson disease).</i></div></div></li><li><div class="bk_ref" id="Trihexyphenidyl.R6">Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52: 2065-76.
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[<a href="/pmc/articles/PMC3992250/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3992250</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20949552" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20949552</span></a>]<div><i>(Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, but none were attributed to agents used for Parkinson disease).</i></div></div></li><li><div class="bk_ref" id="Trihexyphenidyl.R7">Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology 2013; 144: 1419-25,1425.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/23419359" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23419359</span></a>]<div><i>(In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, but none of the 96 were attributed to an agent used to treat Parkinson disease).</i></div></div></li><li><div class="bk_ref" id="Trihexyphenidyl.R8">Drugs for Parkinson's disease. Treat Guidel Med Lett 2013; 11 (135): 101-6.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/24165688" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24165688</span></a>]<div><i>(Concise review of recommendations for therapy of Parkinson disease with description of mechanisms of action, efficacy and adverse events). </i></div></div></li><li><div class="bk_ref" id="Trihexyphenidyl.R9">Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America: an analysis of published reports. Ann Hepatol 2014; 13: 231-9.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/24552865" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24552865</span></a>]<div><i>(Among 176 reports of drug induced liver injury from Latin America published between 1996 and 2012, none were attributed to an agent to treat Parkinson disease).</i></div></div></li><li><div class="bk_ref" id="Trihexyphenidyl.R10">Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.
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[<a href="/pmc/articles/PMC4446235/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4446235</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25754159" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25754159</span></a>]<div><i>(Among 899 cases of drug induced liver injury from the US enrolled in a prospective database between 2004 and 2012, none were attributed to an agent used to treat Parkinson disease).</i></div></div></li></ul></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK547977_pubdet_">Publication Details</h2><h3>Publication History</h3><p class="small">Last Update: <span itemprop="dateModified">July 20, 2017</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="https://www.niddk.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Institute of Diabetes and Digestive and Kidney Diseases</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Trihexyphenidyl. [Updated 2017 Jul 20].<span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/livertox/Triheptanoin/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/livertox/Trilaciclib/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="boxed-text" id="figobTrihexyphenidylBPI"><div id="Trihexyphenidyl.BPI" class="box boxed-text-box whole_rhythm hide-overflow"><p>
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<b>REPRESENTATIVE TRADE NAMES</b>
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</p><p>Trihexyphenidyl – Generic, Artane®</p><p>
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<b>DRUG CLASS</b>
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</p><p>Antiparkinson Agents</p><p>
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<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Trihexyphenidyl" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">COMPLETE LABELING</a>
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</p><p>Product labeling at DailyMed, National Library of Medicine, NIH</p></div></article><article data-type="table-wrap" id="figobTrihexyphenidylT1"><div id="Trihexyphenidyl.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK547977/table/Trihexyphenidyl.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Trihexyphenidyl.T1_lrgtbl__"><table><thead><tr><th id="hd_h_Trihexyphenidyl.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">DRUG</th><th id="hd_h_Trihexyphenidyl.T1_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">CAS REGISTRY NUMBER</th><th id="hd_h_Trihexyphenidyl.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">MOLECULAR FORMULA</th><th id="hd_h_Trihexyphenidyl.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">STRUCTURE</th></tr></thead><tbody><tr><td headers="hd_h_Trihexyphenidyl.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Trihexyphenidyl</td><td headers="hd_h_Trihexyphenidyl.T1_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://pubchem.ncbi.nlm.nih.gov/substance/134974246" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">144-11-6</a>
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</td><td headers="hd_h_Trihexyphenidyl.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">C20-H31-N-O</td><td headers="hd_h_Trihexyphenidyl.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<div class="graphic"><img src="/books/NBK547977/bin/Trihexyphenidyl_Structure.jpg" alt="Trihexyphenidyl Chemical Structure" /></div>
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