トリヘキシフェニジル

Treatment of acute overdose involves symptomatic and supportive therapy. Gastric lavage or other methods to limit absorption should be instituted. A small dose of diazepam or a short-acting barbiturate may be administered if CNS excitation is observed. Phenothiazines are contraindicated because the toxicity may be intensified due to their antimuscarinic action, causing coma. Respiratory support, artificial respiration or vasopressor agents may be necessary. Hyperpyrexia must be reversed, fluid volume replaced and acid-balance maintained. Urinary catheterization may be necessary. It is not known if Trihexyphenidyl is dialyzable. (L1712)

When trihexyphenidyl hydrochloride is used concomitantly with levodopa, the usual dose of each may need to be reduced. Careful adjustment is necessary, depending on side effects and degree of symptoms control. /Trihexylphenidyl hydrochloride/

...CENTRALLY ACTING ANTICHOLINERGIC AGENTS THAT MAY EXACERBATE TARDIVE DYSKINESIA /CAUSED BY CHLORPROMAZINE/ INCL...TRIHEXYPHENIDYL.

Trihexyphenidyl, applied in doses of 30 and 50 mg/kg (ip), did not influence the electroconvulsive threshold per se but when combined with valproate, strongly enhanced its anticonvulsant activity against maximal electroshock-induced seizures /in mice/ lowering the ED50 from 206 to 103 and 46 mg/kg, respectively. The chimney test and retention testing in mice revealed that administration of ... trihexyphenidyl at 30 mg/kg (ip) together with valproate in doses of 130 or 103 mg/kg (ip), respectively, resulted in motor impairment and caused impairment of long-term memory, similar to the effects of valproate alone, when applied at its ED50 against maximal electroshock. ... trihexyphenidyl /did not/ alter the total level of valproate in plasma. ...

Trihexyphenidyl has not been reported to cause serum aminotransferase elevations, but it has not been evaluated for effects on serum enzyme levels in a prospective manner. Trihexyphenidyl was cited as the cause of two cases of acute liver injury resulting in death in the Japanese literature, but few details were given and there have been no other reports of such injury in the literature in the subsequent 40 years. Thus, trihexyphenidyl must be a very rare cause of liver injury, if it occurs at all.

Adverse effects of trihexyphenidyl are frequently dose-dependent but usually decrease over time as tolerance develops and the body adapts to the drug. Even with all of the adverse effects considered, trihexyphenidyl demonstrated dramatic and consistent improvement of neurologic defects in people between the ages of 16 and 86 over a 5-year course. Confusion and delirium frequently occur in older patients or patients with psychiatric disorders.

Signs and Symptoms of Overdose

Trihexyphenidyl is a selective M1 muscarinic acetylcholine receptor antagonist. It is able to discriminate between the M1 (cortical or neuronal) and the peripheral muscarinic subtypes (cardiac and glandular). Trihexyphenidyl partially blocks cholinergic activity in the CNS, which is responsible for the symptoms of Parkinson's disease. It is also thought to increase the availability of dopamine, a brain chemical that is critical in the initiation and smooth control of voluntary muscle movement.

/SIGNS AND SYMPTOMS/ ... In a group of 22 psychiatric patients receiving long-term antipsychotic medication concurrently with trihexyphenidyl the effects of trihexyphenidyl withdrawal were studied double-blind and placebo controlled. Anxiety, psychotic symptoms, extrapyramidal symptoms and salivary flow were monitored. Blood pressure, pulse, sleep duration, weight and body temperature were recorded daily. The result was a recognizable withdrawal syndrome indicated by an increase in anxiety with various physical complaints, as well as evidence of orthostatic hypotension and tachycardia. A temporary deterioration was noted in psychotic symptomatology and extrapyramidal symptoms. The majority of the parameters regained baseline values, indicating the symptoms were related to the discontinuation of trihexyphenidyl and supporting the existence of a withdrawal syndrome.

/SIGNS AND SYMPTOMS/ In Brazil, the medicinal misuse of trihexyphenidyl has been observed among several segments of society. The present study was conducted in the city of Sao Paulo during 2002 to characterize this abuse. A sample of 21 users and 16 ex-users was interviewed using qualitative methodology; the subjects were single, unemployed, male polydrug users, who used trihexyphenidyl in order to attain states of mental alterations, mainly hallucinations and deliriums. Trihexyphenidyl is consumed in association with alcohol, other licit drugs (benzodiazepines), or illicit drugs, impairing cognitive functions such as memory, attention, and learning, intervening with some activities of users' daily life.

/CASE REPORTS/ ... Two case reports of trihexyphenidyl abuse /are described/. In one of the cases a double-blind, placebo-controlled withdrawal was conducted and monitored on a number of physiological parameters and the Hamilton Anxiety Rating Scale. A recognizable withdrawal syndrome followed discontinuation of the drug. ...

/CASE REPORTS/ ... The case presented is of anti-cholinergic abuse by a chronic schizophrenic who abused trihexyphenidyl, up to 200 mg per day, to achieve an euphoric effect. The drug was partly prescribed in psychiatric clinics, but mostly bought in the drugstore. The discontinuance of trihexyphenidyl produced anxiety, which was relieved by anxiolytics. The patient also feigned extrapyramidal symptoms to get anticholinergic injections during drug abstinence. ...

For more Human Toxicity Excerpts (Complete) data for TRIHEXYPHENIDYL (13 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

trihexyphenidyl

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Neurotoxicity/ An amnesic effect ... induced by trihexyphenidyl and biperiden, clinically used in the parkinsonism and schizophrenic patients, /was studied/ by using passive avoidance tasks. Both of these drugs (0.1-10 mg/kg, sc) showed dose-dependent amnesic effects in the acquisition and retrieval phases. However, the effect induced by trihexyphenidyl was transient, whereas that of biperiden was long-lasting. To clarify the reason for the different duration of the amnesic activity, binding to the muscarinic receptor was examined. In the Scatchard analysis, trihexyphenidyl competed with [(3)H]quinuclidinyl benzilate ([(3)H]QNB) on the muscarinic receptor (showed increased K(d) and unchanged B(max) value), while biperiden decreased [(3)H]QNB binding (B(max) value) significantly. Furthermore, in an exchange assay for receptor inactivation, trihexyphenidyl binding to muscarinic receptors was exchanged by [(3)H]QNB completely, but biperiden decreased the exchangeable binding of [(3)H]QNB in a dose dependent manner (0.1-100 nM). ...

/LABORATORY ANIMALS: Neurotoxicity/ The purpose of the present study was to make a comparative assessment of potential cognitive effects of benactyzine (0.3 mg/kg), biperiden (0.11 mg/kg), caramiphen (10 mg/kg), procyclidine (3 mg/kg), and trihexyphenidyl (0.12 mg/kg) separately and each in combination with physostigmine (0.1 mg/kg). The results showed that benactyzine, caramiphen, and trihexyphenidyl reduced rats' innate preference for novelty, whereas biperiden and procyclidine did not. When benactyzine, caramiphen, and trihexyphenidyl were combined with physostigmine the cognitive impairment disappeared. This counteracting effect, however, caused changes in locomotor and rearing activities not seen by each drug alone. Acetylcholinesterase inhibitors and anticholinergics used as prophylactics can offset each other, but exceptions are observed in a previous study when a very potent anticholinergic (scopolamine) or a high dose of procyclidine still results in cognitive deficits in spite of coadministration with physostigmine.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl trihexyphenidyl hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Trihexyphenidyl hydrochloride/

Synthetic antispasmodic ... adjunct in the treatment of all forms of parksinonism (postencephalitic, arteriosclerotic, and idiopathic) /Trihexylphenidyl hydrochloride/

THERAP CAT: Antiparkinsonian /Trihexylphenidyl hydrochloride/

MEDICATION

Use (kg; approx.) in Germany (2009): >10

Indicated for the treatment of parkinson's disease and extrapyramidal reactions caused by drugs.

ACETOPHENONE & PIPERIDINE ARE CAUSED TO UNDERGO MANNICH CONDENSATION WITH FORMALDEHYDE... 3-PIPERIDINOPROPIOPHENONE THUS PRODUCED IS ISOLATED & SUBJECTED TO TYPICAL GRIGNARD REACTION WITH CYCLOHEXYLMAGNESIUM CHLORIDE TO YIELD...TRIHEXYPHENIDYL BASE. HYDROCHLORIDE IS...PREPD BY...PPTN WITH...HYDROGEN CHLORIDE. /HCL/

Adamson, Wilkinson, US 2682543 (1954 to Burroughs Wellcome); Denton, US 2716121 (1955 to American Cyanamide). /Trihexyphenidyl hydrochloride/

Trade Names. Artane (Lederle), Bentex (Steinhard), Broflex (Bio-Med), Pargitan (KabiVitrum), Parkinane (Lederle), Triphenidone (Toho). /Trihexylphenidyl hydrochloride/

Oral: Elixir: 2 mg/5 mL Trihexyphenidyl Hydrochloride Elixir (Mikart), (Pharmaceutical Associates), (Pharmaceutical Ventures). Tablets: 2 mg Trihexyphenidyl Hydrochloride Tablets (URL), (Vintage), (Watson), (West-Ward); 5 mg Trihexyphenidyl Hydrochloride Tablets (URL), (Vintage), (Watson), (West-Ward). /Trihexypheridyl hydrochloride/