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Trihexyphenidyl ( Artane, Apo-Trihex, Parkin, Pacitane ), also known as benzhexol, Artane, and trihex, is an antiparkinsonian agent of the antimuscarinic class. It has been in clinical usage for decades.
Contents
1 Uses
2 Contraindications
3 Adverse effects
4 Overdose
5 Interactions
6 Pharmacology
7 History
8 Society and culture
8.1 Recreational use
9 Chemistry
9.1 Stereochemistry
10 Research
11 See also
12 References
Uses
Trihexyphenidyl is used for the symptomatic treatment of Parkinson’s disease in mono and combination therapy. It is active in postencephalitic, arteriosclerotic, and idiopathic forms. The drug is also commonly used to treat extrapyramidal side effects occurring during antipsychotic treatment. It reduces the frequency and duration of oculogyric crises as well as of dyskinetic movements and spastic contractions. Trihexyphenidyl may improve psychotic depression and mental inertia frequently associated with Parkinson’s disease and symptomatic problems caused by antipsychotic treatment. This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (May 2017) ( Learn how and when to remove this template message )
The drug cannot cure Parkinson’s disease, but may provide substantial alleviation of symptoms. An estimated 50 to 75% of people with Parkinson’s disease will react positively and experience a 20 to 30% symptomatic improvement. To increase therapeutic activity trihexyphenidyl is often given concomitantly with levodopa, other antimuscarinic or antihistaminic (e.g. diphenhydramine ) agents. Combination treatment with dopaminergic agonists such as cabergoline is also possible. This is often termed a ‘multidimensional approach’. It has also been prescribed for essential tremor and akathisia. This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (May 2017) ( Learn how and when to remove this template message )
Contraindications
Contradindications include: This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (May 2017) ( Learn how and when to remove this template message )
Hypersensitivity to trihexyphenidyl
Narrow angle glaucoma
Ileus
Caution : People with obstructive diseases of the urogenital tract, people with a known history of seizures and those with potentially dangerous tachycardia
People under 18 yrs. of age should not be treated due to a lack of clinical experience.
People should allow a period to adjust to the dose when first starting trihexyphenidyl and when the dose has been increased or added to a regimen with other drugs because acute somnolence and accumulated fatigue can make it particularly dangerous to operate an automobile, heavy machinery etc.
Adverse effects
Dose-dependent side effects are frequent, but typically lessen over time as the body adapts to the medication. All of the following symptoms considered, Artane has been shown to dramatically and consistently improve neurologic defects in people aged 16-86 over the course of five years.
Central nervous system: drowsiness, vertigo, headache, and dizziness are frequent. With high doses nervousness, agitation, anxiety, delirium, and confusion are noted. Trihexyphenidyl may be abused due to a short acting mood-elevating and euphoric effect. The normal sleep architecture may be altered ( REM sleep depression). Trihexyphenidyl may lower the seizure-threshold.
Peripheral side effects: dry mouth, impaired sweating, abdominal discomfort, nausea, and constipation are frequent. Tachycardia or heart palpitations (fast heart rate) may be noted. Allergic reactions are rare, but may occur. Many of these peripheral symptoms, especially considering an acute increase in anxiety with various physical complaints, as well as evidence of orthostatic hypotension and tachycardia are indicative of withdrawal, especially in people with psychiatric conditions
Eyes: trihexyphenidyl causes mydriasis with or without photophobia. It may precipitate narrow angle glaucoma or cause blurred vision.
Tolerance may develop during therapy which requires dose adjustments.
Striated musculature and weight gain.
Trihexyphenidyl is a pregnancy category C drug. It is advised to only use with caution if benefits outweigh risks.
Overdose
This section needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the section and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. (May 2017)
Trihexyphenidyl (THP) and other antiparkinsonian drugs are known to be substances of abuse. This is true both in abusers of other substances and in chronic schizophrenics, the latter being infrequent abusers of other drugs. Trihexyphenidyl mimics an atropine intoxication with mydriasis, dryness of mucous membranes, red face, atonic states of bowels and bladder, and hyperthermia in high doses. Central consequences are agitation, confusion, and hallucinations. An untreated overdose may be fatal, particularly in children. Premortal signs are respiratory depression and cardiac arrest. A specific antagonist is physostigmine which combines a peripheral and a central action. Carbachol can be used to treat atonic bowel and bladder. The vital functions should be monitored and stabilized. It may be necessary to treat hyperthermia with cooling blankets. Clinical case reports have repeatedly shown overdose of Trihexyphenidyl alongside other substances.
Interactions
This section needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the section and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. (May 2017)
Other anticholinergic drugs (e.g. spasmolytics, antihistamines, TCAs) : Side effects of trihexyphenidyl may be increased.
Quinidine  : Increased anticholinergic action (particular on AV conduction).
Antipsychotics : Long term use of trihexyphenidyl may mask or increase the risk of tardive dyskinesia.
Pethidine (meperidine) : Central effects and side effects of pethidine may be increased.
Metoclopramide  : Action of metoclopramide is decreased.
Alcohol : Risk of serious intoxication.
Pharmacology
The exact mechanism of action in parkinsonian syndromes is not precisely understood, but it is known that trihexyphenidyl blocks efferent impulses in parasympathetically innervated structures like smooth muscles (spasmolytic activity), salivary glands, and eyes ( mydriasis ). In higher doses direct central inhibition of cerebral motor centers may contribute. In very high doses central toxicity as seen in atropine overdose is noted. It binds to the M1 muscarinic receptor
History
Artane, or its generic form Trihexyphenidyl HCL, was approved by the FDA on June 25th, 2003 for the clinical use of all types of parkinsonism.
Society and culture
Recreational use
In a 2008 news report, trihexyphenidyl was seen to be used for recreational purposes among Iraqi soldiers and police, among other prescription drugs. The report states that the drugs were taken to relieve combat stress.
The neurologist Oliver Sacks reports using the drug recreationally in the 1960s. – have been compared in his novel Hallucinations.
Chemistry
Trihexyphenidyl can be synthesized in two ways, one linear and one convergent synthesis.
In the first way, the initial 2-(1-piperidino)propiophenone is synthesized in turn by the aminomethylation of acetophenone using paraformaldehyde and piperidine in a Mannich reaction. In the second step the 2-(1-piperidino)propiophenone is reacted with cyclohexylmagnesium bromide in a Grignard reaction.
Artane linear and convergent synthesis
Stereochemistry
Trihexyphenidyl has a chiral center and two enantiomers. Medications are racemates.
Enantiomers
CAS number: 40520-25-0
CAS number: 40520-24-9
Research
Equivocal preliminary results from small studies exist for:
Other dyskinesias
Huntington’s chorea
Spasmodic torticollis
Dystonia
See also
Biperiden (bicyclic ring)
Cycrimine (cyclopentanyl instead of cyclohexanyl)
Gamfexine
Procyclidine

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