Trihexyphenidyl

Effects

Overview

Trihexyphenidyl (THP, Pacitane, Benzhexol, Trihex, Artane, and others) is an anticholinergic substance of the antimuscarinic class used to treat stiffness, tremors, spasms, and poor muscle control. In high doses, it has been reported to act as a psychedelic and deliriant.[1][2] PW

Trihexyphenidyl (THP, benzhexol, trihex, gilining marketed as Artane and others) is an antispasmodic drug used to treat stiffness, tremors, spasms, and poor muscle control. It is an agent of the antimuscarinic class and is often used in management of Parkinson's disease. It was approved by the FDA for the treatment of Parkinson's in the US in 1949.[1][3] WP

Trihexyphenidyl is a therapeutic alternative on the World Health Organization's List of Essential Medicines.[4] WP

History

History

Trihexyphenidyl has been clinically relevant in trials pertaining to Parkinson's disease since 1949.[5] WP

In the United States, the Food and Drug Administration (FDA) approved Artane, or its generic form trihexyphenidyl hydrochloride, in June 2003, for the clinical use of all types of parkinsonism.[1] WP

Legal status

Pharmacology

Pharmacodynamics

Trihexyphenidyl is an anticholinergic. It is specifically an antimuscarinic and acts as a non-selective antagonist of all five muscarinic acetylcholine receptors. However, its antagonistic activity is much stronger at the muscarinic acetylcholine M₁ and M₄ receptors, and it can be described as selective for these receptors.[6][7] WP

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. WP

It possibly also binds to dopamine receptors.[8] WP

Pharmacokinetics

Trihexyphenidyl is rapidly absorbed from the gastrointestinal tract. Trihexyphenidyl exhibits high permeability, with absorption occurring primarily via passive diffusion. It is predicted to belong to Biopharmaceutics Drug Disposition Classification System (BDDCS) class I based on structural parameter modeling. Trihexyphenidyl has also been described in the literature as a Biopharmaceutics Classification System (BCS) class I drug. 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.[9–14] WP

Chemistry

Formula

C20H31NO PC

CAS number

144-11-6 PC

Molar mass (g/mol)

301.5 PC

IUPAC name (computed by PubChem)

1-cyclohexyl-1-phenyl-3-piperidin-1-ylpropan-1-ol PC

SMILES

C1CCC(CC1)C(CCN2CCCCC2)(C3=CC=CC=C3)O PC

InChIKey

HWHLPVGTWGOCJO-UHFFFAOYSA-N PC

PubChem CID

5572

Pop culture

No references added yet.

References

1. Journal / agency New Drug Application Approval Notice" (PDF). U.S. Food and Drug Administration. 2003-05-25. Retrieved 2020-08-20
2. Journal / agency Chiappini S, Mosca A, Miuli A, Semeraro FM, Mancusi G, Santovito MC, Di Carlo F, Pettorruso M, Guirguis A, Corkery JM, Martinotti G, Schifano F, Di Giannantonio M. Misuse of Anticholinergic Medications: A Systematic Review. Biomedicines. 2022 Feb 1;10(2):355. doi: 10.3390/biomedicines10020355. PMID: 35203563
3. Other TGA eBS - Product and Consumer Medicine Information Licence
4. Other The selection and use of essential medicines, 2025: WHO Model List of Essential Medicines, 24th list. 2025
5. Journal / agency Doshay LJ, Constable K. Artane therapy for parkinsonism; a preliminary study of results in 117 cases. Journal of the American Medical Association. August 1949. doi:10.1001/jama.1949.02900520003002 · PMID 18137284
6. Journal / agency Lakstygal AM, Kolesnikova TO, Khatsko SL, Zabegalov KN, Volgin AD, Demin KA, Shevyrin VA, Wappler-Guzzetta EA, Kalueff AV. DARK Classics in Chemical Neuroscience: Atropine, Scopolamine, and Other Anticholinergic Deliriant Hallucinogens. ACS Chemical Neuroscience. May 2019. doi:10.1021/acschemneuro.8b00615 · PMID 30566832
7. Journal / agency Giachetti A, Giraldo E, Ladinsky H, Montagna E. Binding and functional profiles of the selective M1 muscarinic receptor antagonists trihexyphenidyl and dicyclomine. British Journal of Pharmacology. September 1986. doi:10.1111/j.1476-5381.1986.tb11123.x · PMID 2432979 · PMC1917044
8. Journal / agency Berke JD, Hyman SE. Addiction, dopamine, and the molecular mechanisms of memory. Neuron. March 2000. doi:10.1016/S0896-6273(00)81056-9 · PMID 10774721
9. Other Trihexyphenidyl Hydrochloride
10. Journal / agency Lu C, Fu K, Cao K, Wei J, Zhou J, Zhao D, Li N, Lu Y, Chen X, Zhang Y. Permeability and transport mechanism of trihexyphenidyl hydrochloride in Caco-2 cell monolayer model with a validated UPLC-MS/MS method. Journal of Pharmaceutical and Biomedical Analysis. January 2020. doi:10.1016/j.jpba.2019.112924 · PMID 31672580
11. Journal / agency Golfar Y, Shayanfar A. Prediction of Biopharmaceutical Drug Disposition Classification System (BDDCS) by Structural Parameters. Journal of Pharmacy & Pharmaceutical Sciences. 2019. doi:10.18433/jpps30271 · PMID 31287788
12. Journal / agency Benet LZ, Broccatelli F, Oprea TI. BDDCS applied to over 900 drugs. The AAPS Journal. December 2011. doi:10.1208/s12248-011-9290-9 · PMID 21818695 · PMC3231854
13. Other Watson Laboratories Inc. trihexyphenidyl hydrochloride tablets, USP. prescribing information. Corona, CA; 2005 May
14. Other AHFS drug information. 2006

Text and values on this page are quoted from PsychonautWiki (CC BY-SA 4.0), Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.