Trihexyphenidyl. Trihexyphenidyl (Trihexyphenidyl) Trihexyphenidyl Latin name

Systematic (IUPAC) name: (RS)-1-cyclohexyl-1-phenyl-3-(1-piperidyl) propan-1-ol
Legal status: Available by prescription only
Usage: oral, tablets or syrup
Half-life: 3.3-4.1 hours
Formula: C20H31NO
Mol. mass: 301.466 g/mol

Cyclodol/Trihexyphenidyl (Artan, Aro-Trihex, Parkin, Pacitane), also known as Benzhexol and Trihex, is an antiparkinsonian drug of the antimuscarinic class. The drug has been used in clinical practice for many decades. It is available as the hydrochloride salt.

Pharmacology

The exact mechanism of parkinsonism syndromes is still not known. Trihexyphenidyl blocks efferent impulses in parasympathetically innervated structures such as smooth muscles (antispasmodic activity), salivary glands, and eyes (mydriasis). At higher doses, direct central inhibition of the motor centers of the brain can be observed. When taken in very high doses, there is a central toxicity observed with an overdose of atropine. Cyclodol binds to muscarinic M1 receptors and possibly to dopamine receptors.

Pharmacokinetics

Trihexyphenidyl is rapidly absorbed from the gastrointestinal tract. After oral administration, the drug begins to act within 1 hour. The peak of activity is observed after 2-3 hours. The duration of action of one single dose is from 6 to 12 hours, depending on the dose. Cyclodol is excreted in the urine, probably unchanged. More precise data in animals and humans have not yet been determined.

Cyclodol indications for use

Trihexyphenidyl is used for the symptomatic treatment of Parkinson's disease, including as part of combination therapy. It is active in postencephalitic, atherosclerotic and idiopathic forms of the disease. The drug is also widely used to treat extrapyramidal side effects that occur during treatment with antipsychotic drugs. Cyclodol reduces the frequency and duration of oculogyric crises, as well as dyskinetic movements and spastic contractions. The drug may also act on excessive salivation. Trihexyphenidyl may improve the symptoms of psychotic depression and mental inertia often associated with Parkinson's disease and symptomatic problems caused by the use of antipsychotics. The drug cannot completely cure Parkinson's disease, but it can significantly reduce its symptoms. It is estimated that 50 to 75% of patients with Parkinson's disease respond positively to treatment, and experience a 20-30% symptomatic improvement. To increase therapeutic activity, trihexyphenidyl is often taken simultaneously with levodopa, other antimuscarinic or antihistamine drugs (for example,). It is also possible combined treatment with dopaminergic agonists, such as. This combined treatment is also called a “multilateral approach”. In addition, the drug is used to treat tremor and akathisia.

Research

Several trials have been conducted with preliminary results regarding the following diseases:

Other dyskinesias

Huntington's chorea

Convulsive torticollis

Dystonia

Trihexyphenidyl does not improve the condition of patients with cerebral palsy and hemiplegia.

Cyclodol contraindications

Hypersensitivity to Trihexyphenidyl

Narrow angle glaucoma

Intestinal obstruction

Special care should be taken: patients with obstructive diseases of the urogenital tract, patients with a known history of seizures and those with potentially dangerous tachycardia.

When starting the use of Trihexyphenidil, as well as when changing the dose or adding other drugs to the treatment regimen, patients should be allowed a period of adjustment to the dose. Drowsiness and accumulated fatigue can be especially dangerous in the case of driving and automation.

Pregnancy and lactation

The safety of Trihexyphenidyl use during pregnancy and lactation has not been established.

Cyclodol side effects

When taking the drug, dose-dependent side effects often appear. Geriatric patients may experience a state of creation confusion or delirium.

From the side of the central nervous system: often - drowsiness, vertigo, dizziness, headache. At high doses, nervousness, agitation, restlessness, delirium and confusion are noted. Due to its short-term effect on mood improvement and sedation, Trihexyphenidyl is included in a group of drugs with potential for abuse. The drug can change the normal architecture of sleep (suppress REM sleep). Trihexyphenidyl may lower the seizure threshold.

Peripheral side effects: blurred vision, dry mouth, impaired sweating, abdominal pain, constipation are common side effects of Cyclodol. Another possible side effect is tachycardia. Allergic skin reactions may develop. Parenteral use may lead to the development of orthostatic hypotension.

Eyes: Trihexyphenidyl causes pupillary dilation with or without photophobia. The drug can accelerate the development of narrow-angle glaucoma.

During therapy, tolerance may develop, which requires dose adjustment.

Interactions

Other anticholinergic drugs (eg, antispasmodics, antihistamines, TCAs) may increase the side effects of Trihexyphenidil.

Quinidine: Increased anticholinergic action.

Antipsychotics: Long-term use of Trihexyphenidyl may mask or increase the risk of tardive dyskinesia.

Pethidine (meperidine): The central effects and side effects of pethidine may be increased.

Metoclopramide: The effect of metoclopramide is reduced.

Alcohol: Risk of serious intoxication.

Cyclodol instructions for use

Parkinson's disease: 1 mg of the drug is taken on the first day. Then every 3 days the dose is increased by 2-6 mg until a dose of 10 mg is reached. In post-encephalitic cases, the drug can be used in doses up to 15 mg, however, side effects such as excessive dry mouth or nausea may occur. To improve tolerance, Trihexyphenidyl can be taken in 3 divided doses.

Extrapyramidal side effects: as a rule, it is necessary to use from 5 to 15 mg of the drug per day in 2 or 3 divided doses. For some patients, however, taking the drug per day at a dose of 1 mg is successful.

Overdose

Trihexyphenidil overdose symptoms mimic atropine intoxication associated with mydriasis, dry mucous membranes, facial flushing, atonic bowel and bladder conditions, and hyperthermia (when taken in high doses). The central effects are associated with agitation, confusion and hallucinations. If left untreated, overdose can be fatal, especially in children. Death signals are respiratory depression and cardiac arrest. The specific antagonist of cyclodol is physostigmine, which combines peripheral and central action. Carbachol can be used to treat atony of the intestines and bladder. Vital functions must be checked and stabilized.

recreational use

A 2008 news report states that trihexyphenidyl, among other drugs, was used recreationally by Iraqi soldiers and police. The report says that the drug was used to facilitate the fight against stress. Neurologist Oliver Sachs reports recreational use of the drug in the 1960s. Trihexyphenidyl can be used in almost all known ways, mixed with opium for smoking, and also used to enhance the effects of morphine, heroin, etc. Like other structurally similar substances such as dicycloverine/dicyclomine, scopolamine, benztropine, and others, cyclodol can be used recreationally for a variety of purposes. Some people use cyclodol to combat excessive sweating, to speed up sleep, and for other purposes. Any off-label use of any medicinal product may be associated with risks. Cyclodol is not used for its intended purpose for the following purposes:

1. As a hallucinogen (an anticholinergic and delirium-inducing agent): some users use dangerously high doses of the substance to induce delusions and hallucinations, similar to datura and belladonna. This practice is extremely dangerous and can lead to death through several different mechanisms, ranging from dehydration to hyperthermia and accidents. An example of the latter is cited in From Chocolate to Morphine and elsewhere. Often, people who have taken huge doses of anticholinergics seek water sources to quench their thirst, which occurs when using the drug, and drown in ponds. Some of this group of users specifically use the drug to see realistic hallucinations and/or feel like flying.

2. As a stimulant or mood enhancer: at significantly lower doses, from sub-therapeutic to elevated, trihexyphenidyl can exhibit a marked stimulant effect. As with many anticholinergics, such as ethanolamine and first-generation alkylamine antihistamines, in some people, particularly the elderly, cyclodol can cause dopaminergic and atropine-like excitatory effects without much CNS depression. One of the results of this use of the drug is euphoria. References can be found in current literature on this topic to the use of cyclodol in combination with caffeine, other natural stimulants, or centrally acting stimulants. Pure amphetamine-like stimulation with anticholinergics is unlikely, but the observed effects with higher doses and a change in the method of administration can lead to a characteristic anticholinergic euphoria when administered parenterally, as well as an interesting combination of stimulant (most often centrally acting like amphetamines) and depressant (associated with drugs ranging from barbiturates to opioids and beta-blockers or in some cases antihistamines) exposure. Many of the effects of Trihexyphenidyl are enhanced by the use of centrally acting stimulants.

3. As a daytime non-benzodiazepine tranquilizer/sedative: The desired effect is achieved at doses much closer to the therapeutic dose. Users can change the way the drug is administered, either by injection or as a smoking mixture. Some people take the drug orally as a remedy for insomnia, although for many people it has the opposite effect. In the police and armed forces of Iraq, the drug is used as a sedative.

4. As a euphoriant (dopaminergic): therapeutic or slightly elevated doses may also exhibit marked antidepressant effects in many people, in addition to anxiolytic effects with improved social interaction and sociability. This is due to the combined effect on changes in the acetylcholine / dopamine site in the CNS in favor of the latter and some structural similarities with tricyclic antidepressants. A similar antidepressant effect has been observed with scopolamine, which is why these drugs are being investigated for their medical use in treatment-resistant depression. The anticholinergic-antidepressant relationship may also be considered in the cases of orphenadrine, cyclobenzaprine, and dicycloverine/dicyclomine, which are structurally related to tricyclic antidepressants, although tricyclic antidepressants exhibit more pronounced effects and have more serious side effects. The use of Trihexyphenidyl as a self-medication for depression, as well as its use in non-depressed individuals to achieve euphoria, is mentioned in passing in the Diagnostic and Statistical Manual of Mental Illness, Volume IV. In recent decades, studies have been conducted on the abuse of anticholinergics in general.

5. As an opioid potentiator: Trihexyphenidyl is also used similarly to some first-generation antihistamines such as diphenhydramine, tripelennamine, brompheniramine, hydroxyzine, cyproheptadine, some anticholinergic eye drops, and similar drugs to increase the effectiveness of narcotic analgesics in preclinical users and individuals wishing to improve pain relief and euphoria from a given dose of the drug. One of the dangerous side effects of this kind of combination can be constipation, leading to intestinal obstruction. Trihexyphenidyl is very similar in action to dicyclomine, and both drugs are used in clinical trials as active placebos for morphine, levorphanol, and other sedatives and opioids.

6. As an aphrodisiac: Trihexyphenidyl exhibits a marked aphrodisiac effect, at least for some users, in potency between dicycloverine/dicyclomine and methaqualone. There is information that dicycloverine/dicyclomine enhances libido, and that trihexyphenidyl is more potent and, like dicycloverine/dicyclomine, also has a surprisingly rapid onset of action when taken orally, buccally and sublingually. The drug exhibits an excitatory effect and is more anxiolytic than dicycloverine / dicyclomine, and lasts longer; this also applies to the sedative effect.

7. Intended Use: Trihexyphenidyl is used to counter the effects of other drugs.

8. Military Premedication: The use of high doses of Trihexyphenidyl (often along with stimulants and/or alcohol) has been reported in the Middle East and elsewhere, particularly among soldiers and police, to prepare for engagement in conflict. This usage is reminiscent of the berserkers (warriors) of ages past, who were known to use plant-based anticholinergics such as henbane and belladonna for an "uncontrollable frenzy" effect.

Dosage forms and availability

Syrup, as hydrochloride: 2 mg/5 ml (480 ml)

Tablets, as hydrochloride: 2 mg, 5 mg

Chemistry

Trihexyphenidyl, 1-cyclohexyl-1-phenyl-3-piperidineopropan-1-ol, is synthesized in two ways (linear and convergent synthesis): In the first case, the initial product, 2-(1-piperidino) propiophenone, is synthesized, in turn, by aminomethylation of acetophenone with paraformaldehyde and piperidine in the so-called Mannich reaction. In the second step, 2-(1-piperidino) propiophenone is reacted with cyclohexylmagnesium bromide in a Grignard reaction.

Trihexyphenidyl hydrochloride (trihexyphenidyl)

Composition and form of release of the drug

Tablets white, round, flat-cylindrical, with a chamfer.

Excipients: sucrose (white sugar) - 78.4 mg, potato starch - 18.6 mg, calcium stearate - 1 mg.

10 pieces. - cellular contour packings (1) - packs of cardboard.
10 pieces. - cellular contour packings (2) - packs of cardboard.
10 pieces. - cellular contour packings (3) - packs of cardboard.
10 pieces. - cellular contour packings (4) - packs of cardboard.
10 pieces. - cellular contour packings (5) - packs of cardboard.
10 pieces. - cellular contour packs (100) - cardboard boxes (for hospitals).
10 pieces. - cellular contour packs (200) - cardboard boxes (for hospitals).
10 pieces. - cellular contour packaging (300) - cardboard boxes (for hospitals).
10 pieces. - cellular contour packaging (400) - cardboard boxes (for hospitals).
10 pieces. - cellular contour packs (600) - cardboard boxes (for hospitals).

pharmachologic effect

Antiparkinsonian drug. It has a strong central n-anticholinergic effect, as well as a peripheral m-anticholinergic effect. The central action helps to reduce or eliminate movement disorders associated with extrapyramidal disorders.

In parkinsonism, it reduces tremor, to a lesser extent affects rigidity and bradykinesia.

It has an antispasmodic effect, which is associated with anticholinergic activity and direct myotropic action.

Indications

Parkinsonism (idiopathic, postencephalitic, atherosclerotic, due to side effects of drugs; as monotherapy and in combination with levodopa), Little's disease, spastic paralysis associated with lesions of the extrapyramidal system.

Contraindications

Urinary retention, prostate adenoma, glaucoma, atrial fibrillation, obstructive gastrointestinal diseases,.

Dosage

Set individually. The initial dose is 0.5-1 mg / day. Then, if necessary, every 3-5 days the dose is gradually increased by 1-2 mg until the optimal therapeutic effect is achieved; the multiplicity of reception - 3-5 times / day.

For hypersalivation prior to treatment, trihexyphenidyl should be taken after meals. With the development of dryness of the oral mucosa during treatment, trihexyphenidyl is prescribed before meals (if nausea does not occur).

Maximum doses: when taken orally, a single dose is 10 mg, a daily dose is 20 mg.

Side effects

Others: purulent parotitis (due to xerostomia).

drug interaction

With the simultaneous use of drugs with anticholinergic action, it is possible to increase anticholinergic effects.

With simultaneous use with levodopa, the absorption and Cmax of levodopa in the blood decreases.

With simultaneous use with reserpine, the antiparkinsonian effect of trihexyphenidyl decreases, tk. the reserves of catecholamines in the central nervous system are depleted. As a result, cholinergic neurons are activated, and the parkinsonism syndrome is enhanced.

With simultaneous use, a decrease in plasma concentration is possible, apparently associated with a violation of absorption from the gastrointestinal tract.

special instructions

Use with caution in diseases of the heart, kidneys or liver, arterial hypertension.

During treatment, intraocular pressure should be regularly monitored.

With long-term treatment, the intensity of adverse reactions due to the anticholinergic activity of trihexyphenidyl usually decreases; possible development of drug dependence.

With the simultaneous use of trihexyphenidyl with levodopa, correction of the dosing regimen is required.

Influence on the ability to drive vehicles and control mechanisms

Pregnancy and lactation

Trihexyphenidyl is contraindicated for use in pregnancy.

For impaired renal function

Use with caution in kidney disease.

For impaired liver function

Use with caution in liver diseases.

Use in the elderly

In patients over the age of 60 years, dose selection of trihexyphenidyl is carried out with extreme caution due to the high likelihood of hypersensitivity reactions.

It is not always possible to buy a prescribed medicine without problems at the nearest pharmacy, or its cost is too expensive, and treatment is necessary. In such cases, it is useful to know the synonyms of drugs that can replace the prescribed medication.

The article will help you figure out what are the analogues of Trihexyphenidyl, what are their features and pricing policy.

Instructions for use

Trihexyphenidyl is an antiparkinsonian drug in the form of tablets.

A medicine is used for Little's disease or parkinsonism, as well as to reduce the effects of paresis and eliminate tremor or spastic paralysis.

Can be used in the treatment of extrapyramidal disorders due to medication, including neuroleptics.

The drug has an anticholinergic effect of the central and peripheral nervous system, is able to relax muscles, thereby significantly reducing trembling of the limbs.

It has a weaker effect on bradykinesia and rigidity. Due to the ability to block choline, the medicine reduces the production of saliva and sweat. The drug is characterized by the properties of a local anesthetic.

The substance is quickly absorbed from the digestive tract, so an hour passes from taking the pill to the manifestation of the action. The action lasts from 3 to 5 hours. After the injection, the action begins after 10-15 minutes and lasts up to 12 hours.

Trihexyphenidyl crosses the placental and blood-brain barrier. It is excreted from the body in the form of metabolites along with urine.

The dosage is prescribed by the attending physician individually.

Initially, no more than 1 mg per day is prescribed. For optimal treatment effect dosage increased every 3-5 days. The dosage is divided into 3-5 doses during the day before or after meals, as recommended by the doctor. The maximum single dose is 10 mg. People who have crossed the threshold of 60 years require special attention from doctors when taking the drug.

During long-term use, intraocular pressure should be monitored. The intensity of adverse reactions decreases with time. The drug may be habit-forming.

You can buy the drug from 92 rubles per pack of 50 tablets of 2 mg.

Analogues

Trihexyphenidyl as an active ingredient is part of various drugs. Instructions for use for substitutes are absolutely identical to the original.

Consider analogues of Trihexyphenidyl. Some of them are currently not available for purchase in Russia.

Foreign

Romparkin (Romania)

The medicine is produced in the form of white tablets. One tablet contains 2 mg of the active ingredient. The package contains 5 blisters of 10 tablets each. The initial dose for treatment is 0.5-1 mg per day, over time it can increase to 10 mg.

Tryfen (India)

Dosage form - tablets with 2 mg of active ingredient each. Treatment begins with 1 mg per day and gradually bring the dosage to the minimum effective. The maximum daily dose is 20 mg. The medication is divided into 3-5 times during the day.

Apo-Trihex (Canada)

Available in the form of tablets of 5 mg 50,100 or 500 pieces per pack, and 2 mg 50 or 500 pieces per vial. Reception begins with 1-2 mg per day, and increasing the dose within 3-5 days, bring it to 6-10 milligrams. The drug is taken 3-5 times a day with meals.

Trihexyphenidyl Hydrochloride (India or Italy)

Available in powder form. The minimum dose is 0.5 mg per day. Over time, the dose should be increased to the minimum effective.

The maximum dose of one dose is 10 mg, It is not recommended to take more than 20 milligrams per day. With hypersalivation, the drug is taken after meals, and with dry mouth - before meals.

Parkopan (Germany)

Release form - tablets containing 2 and 5 mg. The package contains 100 tablets. The dose of the drug is selected by the attending physician individually, starting with 1 mg, and bringing to the minimum effective. The daily dose should be ingested in 3-5 doses.

Akineton (Germany)

White round tablets or solution for injection. Tablets are sold in a carton box of 2, 5, 10 blisters, each containing 10 tablets, or 2.5 blisters with 20 tablets.

Active substance - . Adults are prescribed 1 mg several times a day, increasing the dosage every day by 2 milligrams.

The maximum dose is 16 mg, it should be divided into 2-3 doses per day.

Injections are administered slowly intravenously or intramuscularly, 10-20 milligrams are divided into 2-3 injections.

The cost of the drug: 547.00 rubles.

Mendileks (Macedonia)

Round convex tablets on both sides containing 2 mg of the active substance - biperidene chloride. The carton box contains 5 blisters of 10 tablets. The initial dose of the drug is 2 mg for 2 doses. For most patients the optimal daily dose is 3-12 mg and is divided into 3-4 doses. Treatment should not be stopped abruptly due to the risk of withdrawal.

The cost of the drug: 148 rubles.

Russian

Cyclodol

Dosage form - tablets. 25 pieces in a blister and 2 blisters in a cardboard box. It is used orally before or during meals.

At the first dose, no more than 1 mg per day is prescribed.. Over time, the dose increases to 6-10 mg for 3-4 doses per day. Severe cases require increasing the dose to 12-16 milligrams. It is unacceptable to exceed 10 as a single dose and 16 mg as a daily dose.

Price: 21 - 94 rubles.

Comparison of drugs

Most synonyms for the drug Trihexyphenidyl contain trihexyphenidyl as the main active ingredient, with the exception of Mendilex and Akineton (biperidene chloride).

All drugs have the same property - antiparkinsonian action. By blocking choline, drugs can affect the central and peripheral nervous systems.

All analogues also have the same list of contraindications. Drugs are strictly prohibited if at least one of the following points occurs.

• Allergy to the active substance;
• With urinary retention;
• dementia;
• Pulmonary edema;
• Dysfunction and diseases of the gastrointestinal tract;
• Urinary retention;
• Pregnancy (especially the first trimester);
• risk of atrial fibrillation.

Most drugs should not be used by children under 12 years of age.

There are also similar side effects:

• From the nervous system: acute pain in the head and temples, prolonged hallucinations, disorientation.
• Effects caused by anticholinergic action: dryness of the mouth, reduced vision, increased intraocular pressure, difficult urination and disruption of the heart (tachycardia).
• Allergy: rash on the skin surface of a different nature and purulent parotitis.

With prolonged use, side effects become less pronounced.

Country of origin

Product group

Antiparkinsonian

Release forms

• 10 - cellular contour packs (5) - packs of cardboard. 10 - strips (5) - packs of cardboard.

Description of the dosage form

• Tablets

pharmachologic effect

Special conditions

Compound

• Trihexyphenidyl 2mg; Auxiliary in-va: calcium stearate monohydrate, potato starch, povidone, crospovidone, sucrose

Trihexyphenidyl indications for use

• Parkinsonism (idiopathic, postencephalitic, atherosclerotic, due to side effects of drugs; as monotherapy and in combination with levodopa), Parkinson's disease, Little's disease, spastic paralysis associated with lesions of the extrapyramidal system.

Trihexyphenidyl contraindications

• Urinary retention, prostate adenoma, glaucoma, atrial fibrillation, obstructive gastrointestinal diseases, pregnancy.

Trihexyphenidyl dosage

Trihexyphenidyl side effects

• From the side of the central nervous system: headache, irritability, delirium, hallucinations, mental disorientation (mainly in patients with atherosclerosis). Effects due to anticholinergic activity: dryness of the oral mucosa, visual disturbances, increased intraocular pressure, constipation, difficulty urinating, tachycardia. Allergic reactions: skin rash. Others: purulent parotitis (due to xerostomia).

drug interaction

Storage conditions

• keep away from children

N.04.A.A.01 Trihexyphenidyl