Trihexyphenidyl

drugbox
IUPAC_name = 1-cyclohexyl-1-phenyl-3-(1-piperidyl)propan-1-ol

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CAS_number = 144-11-6
ATC_prefix = N04
ATC_suffix = AA01
ATC_supplemental =
PubChem = 5572
DrugBank = APRD00070
C=20 | H=31 | N=1 | O=1
molecular_weight = 301.466 g/mol
bioavailability =
protein_bound =
metabolism =
elimination_half-life = 3.3-4.1 hours
pregnancy_category = C US
legal_status = Rx-Only (US)
routes_of_administration = Oral, as tablet or elixir

Trihexyphenidyl, also known as Benzhexol, (sold under the brandnames Aparkan and Artane) is an antiparkinsonian drug of the antimuscarinic class. Chemically, it is a tertiary amine with alcohol, phenyl, and cyclohexyl moieties. It has been in clinical usage for decades. The drug is available as the hydrochloride salt.

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.

Pharmacokinetics

Trihexyphenidyl is rapidly absorbed from the GI-Tract. The onset of action is within 1 hour after oral dosing. The peak activity is noted after 2 to 3 hours. The duration of action of one single dose is 6 to 12 hours in a dose dependent manner. It is excreted in the urine, probably as unchanged drug. More precise data in animals and humans have so far not been determined.

Established 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. Excessive salivation may also respond. Trihexyphenidyl may improve psychotic depression and mental inertia frequently associated with Morbus Parkinson and symptomatic problems caused by antipsychotic treatment.

Therapeutic prospects

The drug hao is not able to cure Morbus Parkinson, but may provide substantial alleviation of symptoms. An estimated 50 to 75% of patients with M. Parkinson 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'.

Investigational uses

Equivocal preleminary results from small studies exist for:
* Other Dyskinesias
* Huntington's Chorea
* Spasmodic Torticollis
*DystoniaTrihexyphenidyl does not improve cerebral palsy and hemiplegia.

Contraindications and cautions

See Biperiden.
* Patients under 18 yrs. of age should not be treated due to a lack of clinical experience.

* Trihexyphenidyl has been reported as a drug of abuse, and while this is uncommon it may be prudent to be cautious in prescribing this drug to patients with a history of drug addiction. The drug has euphoriant and aphrodisiac properties and is smoked, insufflated, swallowed, or dissolved under the tongue and has enhanced activity when injected. Some users report a rush in the genital area when used in such a way as to deliver the dose very quickly and for this and other reasons Artane® and similar drugs are referred to by some as Sexy Trihexy, Tri-Sexual, T. Hex, and Octane.

* Patients should allow a period to adjust to the dose when first adjusting to trihexyphenidyl and when the dose has been increased or added to a regimen with other drugs because acute somnolence and accumulated fatigue can make in particularly dangerous to opeate an automobile, heavy machinery or that containing hot liquids &c.

Pregnancy and lactation

The safe use of Trihexyphenidyl during pregnancy and lactation has so far not been assured.

ide-effects

See Biperiden. Tolerance may develop during therapy which requires dose adjustments.

Interactions

See Biperiden.

Dosage

* Morbus Parkinson : One mg is given on the first day. Increments are usually 2mg every 3 days until 6 to 10mg are reached. In postencephalitic cases up to 15 mg might be necessary, but then excessive dryness of mouth or nausea could be a problem. To increase tolerability Trihexyphenidyl may be given in 3 divided doses.

* Extrapyramidal side effects : Usually, 5 to 15 mg daily are needed in 2 or 3 divided doses. Some patients, however, are successfully treated with as little as 1 mg daily.

Overdose

See Biperiden.

Brand names and dose forms

* Artane : elixir 2mg/5ml, tabletts 2mg and 5mg
* Generics (e.g. Cypress, URL, Watson, West-Ward) : elixir and/or tabletts
* Pacitane "http://www.wyethindia.com/products/pacitane.asp?prodid=7"

External links

* AHFS online database
* http://www.mentalhealth.com/drug/p30-t04.html