Trihexyphenidyl Hydrochloride

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Cat Number

API52493

CAS Number

52-49-3

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CAS Number

52-49-3

EINECS

200-142-5

Storage

Store at room temperature

Synonyms

Trihexyphenidyl HCl; Cyclodol; Parcopane; Romparkin; Cyclodolum; Tremin; Aparkane; Triphedinon; Sedrina; NSC-757357; DTXSID8045802; AO61G82577

Molecular Formula

C20H32ClNO

Molecular Weight

337.9

Smiles

C1CCC(CC1)C(CCN2CCCCC2)(C3=CC=CC=C3)O.Cl

Appearance

White to off-white powder

Melting Point

114-115℃

Relative Density

0.9801

General Description

Trihexyphenidyl hydrochloride is a centrally acting anticholinergic agent used as an adjunct in the management of parkinsonism and drug-induced extrapyramidal disorders. It is available in oral tablets and elixir, functioning as a muscarinic receptor antagonist that restores the balance between dopamine and acetylcholine in the basal ganglia. The drug is particularly useful in patients with tremor-predominant symptoms.

Mechanism of Action

Trihexyphenidyl competitively blocks muscarinic acetylcholine receptors in the central nervous system, specifically within the striatum. By reducing cholinergic overactivity that results from relative dopamine deficiency in parkinsonism, it helps normalize the dopamine-acetylcholine balance. This antagonism improves motor symptoms such as tremor, rigidity, and bradykinesia. The drug has minimal effects on nicotinic receptors and exhibits greater selectivity for central rather than peripheral muscarinic sites.

Application

It is indicated for the treatment of all forms of parkinsonism, including idiopathic Parkinson's disease and postencephalitic parkinsonism, as well as for controlling extrapyramidal symptoms induced by antipsychotic medications. It is particularly effective against tremor and sialorrhea. Due to its anticholinergic side effect profile including dry mouth, blurred vision, constipation, and cognitive impairment, it is generally reserved for younger patients without significant cognitive decline.

In a 7‑month study, rats receiving the anticholinergic drug trihexyphenidyl (THP) showed early cognitive deficits that paradoxically resolved over time. Gene microarray analysis revealed that THP primarily downregulated immune response genes, including those involved in antigen processing and major histocompatibility complex (MHC) class I expression. Chronic THP treatment also induced microgliosis and microglial activation in the hippocampus and cortex, accompanied by pathological misfolded tau lesions. The authors conclude that long‑term exposure to anticholinergic drugs like THP accelerates Alzheimer‑like neurodegeneration through neuroinflammation and suppression of immune‑related pathways, rather than through direct cholinergic toxicity.

Fig. 1 Long-term THP treatment recruits distinct gene expression profiles. (Huang Y, et al., 2016)

References

Huang Y, et al. Long-term trihexyphenidyl exposure alters neuroimmune response and inflammation in aging rat: relevance to age and Alzheimer's disease. J Neuroinflammation. 2016; 13(1):175.

A single small, double‑blind, placebo‑controlled crossover trial (16 children with predominant dystonic cerebral palsy) provided low‑quality evidence that trihexyphenidyl did not improve dystonia scores (Barry Albright Dystonia Scale) or upper limb function, but may increase adverse effects (RR 2.54). Participation in daily living activities improved on some measures, but pain and quality of life were not reported. The Cochrane review authors conclude that insufficient evidence exists to support or refute the use of trihexyphenidyl for dystonia in cerebral palsy; larger, well‑designed trials are needed.

Fig. 2 Study flow diagram.(Harvey AR, et al., 2018)

References

Harvey AR, et al. Trihexyphenidyl for dystonia in cerebral palsy. Cochrane Database Syst Rev. 2018; 5(5):CD012430.

Does Trihexyphenidyl Hydrochloride require protection from light during storage?

Yes, it is photosensitive. Prolonged UV exposure can cause photodegradation. Store in light-resistant, tightly sealed containers, preferably amber glass.

What is the recommended storage temperature for Trihexyphenidyl Hydrochloride?

Store at controlled room temperature (15-25°C). Avoid excessive heat above 30°C, as it can cause softening or melting of the crystalline powder.

Is Trihexyphenidyl Hydrochloride hygroscopic, and how is this managed?

It is slightly hygroscopic. Storage in tightly sealed containers with desiccant is recommended, especially in high-humidity environments, to prevent caking.

How is the impurity trihexyphenidyl N-oxide monitored during stability?

This oxidative degradation product is quantified using a validated HPLC method, ensuring it remains below ICH qualification thresholds throughout shelf life.