Biperiden

311.46106

311.46

208-184-6

0FRP6G56LD

759145

DTXSID6022680

Crystals

N04AA02|N - Nervous system

2933399090

23.5

4.1

Solid

1.1±0.1 g/cm3

114 °C

462.1±40.0 °C at 760 mmHg

224.5±26.0 °C

1.583

H2O: 25.1 mg/L

Biperiden hydrochloride tablets should be stored in tight, light-resistant containers at 15-30 deg C.

5.42 mm Hg at 25 deg C (est)

Oral-rat LD50: 750 mg/kg; Oral-Mouse LD50: 530 mg/kg

Flammable; burning produces toxic nitrogen oxide fumes

Henry's Law constant = 2.44X10-10 atm-cu m/mol at 25 °C (est)

pKa = 9.74 (amine) (est)

175.7 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Hydroxyl radical reaction rate constant = 1.79X10-10 cu cm/molec-sec at 25 °C (est)

NONH for all modes of transport

Ventilated, low temperature and dry

P210, P240, P241, P261, P264, P270, P271, P273, P280, P301+P312, P304+P312, P304+P340, P305+P351+P338, P312, P330, P337+P313, P370+P378, P501

H228

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

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

moderately toxic

LD50=760 mg/kg (Orally in rats). Signs of overdose include dilated and sluggish pupils, warm, dry skin, facial flushing, decreased secretions of the mouth, pharynx, nose, and bronchi, foul-smelling breath, elevated temperature, tachycardia, cardiac arrhythmias, decreased bowel sounds, urinary retention, delirium, disorientation, anxiety, hallucinations, illusions, confusion, incoherence, agitation, hyperactivity, ataxia, loss of memory, paranoia, combativeness, and seizures.

Biperiden 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. Despite its use for more than 50 years, there have been no reports of biperiden liver injury in the literature and it must be a very rare cause of liver injury, if it occurs at all.

In rats the pharmacokinetic interactions between the anticholinergic drug biperiden and [3(H)]quinuclidinyl benzylate ([3(H)]QNB) or [3(H)]N-methylscopolamine ([3(H)]NMS) is affected by the sequence in which the drugs are administered. Drug concentrations in various tissues were determined after intravenous administration of [3(H)]QNB or [3(H)]NMS (325 ng kg(-1)). Biperiden (6.4 mg kg(-1)) was administered either 5 min before, concomitantly with or 20 min after injection of [3(H)]QNB or [3(H)]NMS. When biperiden was administered concomitantly with or before [3(H)]QNB, distribution of [3(H)]QNB among the regions of the brain and other tissues was reduced; at 4 hr the ratio of the distribution of [3(H)]QNB for experimental animals to that for control animals ranged from 0.15 to 0.9. When biperiden was administered after [3(H)]QNB, the distribution of [3H]QNB in the brain and other tissues was significantly higher than for the other two treatments (P < 0.01). However, for [3(H)]NMS the sequence of administration had no effect on the distribution of the drug in the brain and other tissues except for the kidney. In-vitro, in crude synaptosomal membranes, the amount of [3(H)]QNB at 2 hr relative to the control concentration at equilibrium was 87% when biperiden was added before [3(H)]QNB and 56% when biperiden was added after [3(H)]QNB. In both instances the concentration of [3(H)]NMS reached equilibrium within 30 min. These findings suggest that the difference between the rate constant of association and dissociation at the possible site of action gives rise to the effect of the sequence of administration on the pharmacokinetic interaction.|Concomitant administration of biperiden with other drugs having anticholinergic effects (e.g., opiate agonists, phenothiazines and other antipsychotics, tricyclic antidepressants, quinidine, antihistamines) may increase the risk of adverse anticholinergic effects.|In order to find molecules affected by administration of an antipsychotic drug with an antimuscarinic drug, which is a common prescription used to prevent extrapyramidal adverse effects caused by the antipsychotic drugs, gene expression profiling in the frontal cortex was studied in mice. After 14 days of administration with 2 mg/kg haloperidol, a typical antipsychotic drug, and 2 mg/kg biperiden, a high-affinity antagonist for muscarinic receptors in the brain, approximately 500 mRNAs related to synaptic function were investigated. The levels of the mRNAs related to the ubiquitin-related systems were significantly reduced after the combined administration. However, the separate administration of either haloperidol or biperiden had little effect on the levels of the mRNAs. This result suggests that coadministration of haloperidol and biperiden specifically affects the ubiquitin-related system.

LD50 Dog oral 340 mg/kg /Biperiden hydrochloride/|LD50 Dog iv 222 mg/kg /Biperiden lactate/|LD50 Rat ip 270 mg/kg /Biperiden lactate/|LD50 Rat oral 750 mg/kg|For more Non-Human Toxicity Values (Complete) data for BIPERIDEN (7 total), please visit the HSDB record page.

60%

For use as an adjunct in the therapy of all forms of parkinsonism and control of extrapyramidal disorders secondary to neuroleptic drug therapy.

Biperiden is an oral anticholinergic agent used predominantly in the symptomatic therapy of Parkinson disease and movement disorders. Biperiden has not been associated with serum enzyme elevations during treatment and must be a very rare cause of clinically apparent acute liver injury, if it occurs at all.

Antiparkinson Agents

Biperiden is used for the adjunctive treatment of all forms of parkinsonian syndrome, in which it appears to be more effective in the postencephalitic and idiopathic than in the arteriosclerotic types. Biperiden usually relieves muscle rigidity, reduces sweating and salivation, and improves gait and, to a lesser extent, tremor. Biperiden also is used for the relief of parkinsonian signs and symptoms of antipsychotic agent-induced (e.g., phenothiazines) extrapyramidal reactions. Although it has been used as adjunctive therapy in the management of other disorders of the extrapyramidal system and of unrelated spastic conditions such as multiple sclerosis, cerebral palsy, and spinal cord injuries, the value of the drug in these conditions requires further investigation.|/EXPL THER/ To study the influence of antidotes on tabun-induced neurotoxicity, the rats were injected intramuscularly with organophosphate tabun. The efficacy of choice antidotal treatment consisting of acetylcholinesterase reactivator obidoxime and one of four anticholinergic drugs (atropine, benactyzine, biperiden, scopolamine) was compared. Testing of tabun-induced neurotoxicity progress was carried out using the method Functional observational battery. The experimental animals as well as controls were observed at 24 hours and 7 days following tabun or saline administration. The results were compared to the condition of animals without anticholinergic drug (oxime alone) and control rats that received physiological solution instead of tabun and treatment. Antidotal treatment involving centrally acting anticholinergic drugs (benactyzine, biperiden, scopolamine) showed significantly higher neuroprotective efficacy compared to antidotal treatment containing atropine.|/EXPL THER/ To study the influence of pharmacological pretreatment (PANPAL or pyridostigmine combined with biperiden) and antidotal treatment (the oxime HI-6 plus atropine) on soman-induced neurotoxicity, male albino rats were poisoned with a lethal dose of soman (54 (g/kg im; 100% of LD50 value) and observed at 24 hours and 7 days following soman challenge. The neurotoxicity of soman was evaluated using a Functional observational battery and an automatic measurement of motor activity. Pharmacological pretreatment as well as antidotal treatment were able to eliminate some of soman-induced neurotoxic effects observed at 24 hours following soman poisoning. The combination of pharmacological pretreatment (PANPAL or pyridostigmine combined with biperiden) and antidotal treatment was found to be more effective in the elimination of soman-induced neurotoxicity in rats at 24 hours following soman challenge in comparison with the administration of pharmacological pretreatment or antidotal treatment alone. To compare both pharmacological pretreatments, the combination of pyridostigmine with biperiden seems to be more efficacious to eliminate soman-induced signs of neurotoxicity than PANPAL. At 7 days following soman poisoning, the combination of pharmacological pretreatment involving pyridostigmine and biperiden with antidotal treatment was only able to completely eliminate soman-induced neurotoxic signs. Thus, our findings confirm that the combination of pharmacological pretreatment and antidotal treatment is able not only to protect the experimental animals from the lethal effects of soman, but also to eliminate most soman-induced signs of neurotoxicity in poisoned rats. The pharmacological pretreatment containing pyridostigmine and biperiden appears to be more efficacious to eliminate soman-induced neurotoxic sings than PANPAL.

Isolated instances of mental confusion, euphoria, agitation and disturbed behavior have been reported in susceptible patients. Also, the central anticholinergic syndrome can occur as an adverse reaction to properly prescribed anticholinergic medication, although it is more frequently due to overdosage. It may also result from concomitant administration of an anticholinergic agent and a drug that has secondary anticholinergic actions. Caution should be observed in patients with manifest glaucoma, though no prohibitive rise in intraocular pressure has been noted following either oral or parenteral administration. Patients with prostatism, epilepsy or cardiac arrhythmia should be given this drug with caution. Occasionally, drowsiness may occur, and patients who drive a car or operate any other potentially dangerous machinery should be warned of this possibility. As with other drugs action on the central nervous system, the consumption of alcohol should be avoided during Akineton therapy.|Biperiden should be used with caution or may be contraindicated in patients with conditions in which anticholinergic effects are undesirable. The usual precautions and contraindications associated with antimuscarinics should be observed with biperiden.|Adverse reactions to biperiden are mainly extensions of its anticholinergic effects. Dryness of the mouth and blurred vision are common and are dose related. GI disturbances may occur and can be alleviated by administering the drug with or after meals. Drowsiness, dizziness, and mental confusion occur less frequently. Transient psychotic reactions, euphoria or disorientation, agitation, disturbed behavior, urinary retention, and hematuria have been reported rarely. In some severe cases of parkinsonian syndrome, tremor may increase as spasticity is relieved. In addition, generalized choreiform movements have been reported in at least one patient with parkinsonian syndrome when biperiden was added to levodopa-carbidopa therapy. A reduction in rapid eye movement (REM) sleep, characterized by increased REM latency and decreased percentage of time spent in REM sleep, also has been reported.|It is not known whether biperiden is distributed into milk. Because many drugs are distributed into milk, biperiden should be used with caution in nursing women.|For more Drug Warnings (Complete) data for BIPERIDEN (8 total), please visit the HSDB record page.

Biperiden is a weak peripheral anticholinergic agent. It has, therefore, some antisecretory, antispasmodic and mydriatic effects. In addition, biperiden possesses nicotinolytic activity. The parenteral form of biperiden is an effective and reliable agent for the treatment of acute episodes of extrapyramidal disturbances sometimes seen during treatment with neuroleptic agents. Akathisia, akinesia, dyskinetic tremors, rigor, oculogyric crisis, spasmodic torticollis, and profuse sweating are markedly reduced or eliminated. With parenteral biperiden, these drug-induced disturbances are rapidly brought under control.

Agents used in the treatment of Parkinson's disease. The most commonly used drugs act on the dopaminergic system in the striatum and basal ganglia or are centrally acting muscarinic antagonists. (See all compounds classified as Antiparkinson Agents.)|Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS. (See all compounds classified as Parasympatholytics.)|Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system. (See all compounds classified as Muscarinic Antagonists.)

87% bioavailability|The serum concentration at 1 to 1.5 hours following a single, 4 mg oral dose was 4-5 ng/mL. Plasma levels (0.1-0.2 ng/mL) could be determined up to 48 hours after dosing. Six hours after an oral dose of 250 mg/kg in rats, 87% of the drug had been absorbed.|The subcellular distribution of biperiden (BP), trihexyphenidyl (TP) and (-)-quinuclidinyl benzylate (QNB) in brain, heart and lung following high dose (3.2 mg/kg) iv administration was investigated in rats. The subcellular distribution of BP or TP used clinically conformed with that of QNB, a typical potent central muscarinic antagonist. The concentration-time courses of the brain subcellular fractions for these drugs were of two types which decreased slowly and in parallel to the plasma concentration. The subcellular distribution in the brain and heart was dependent on the protein amount of each fraction. The percent post-nuclear fraction (P2) of the total concentration in the lung was characteristically about 3-5 times larger than that in the heart. It was elucidated that the distribution in the lung differs from that in the brain and heart, with high affinity which is not dependent on the protein amount in the P2 fraction containing lysosomes. On the other hand, at a low dose (650 ng/kg) of 3H-QNB, each fraction as a percentage of the total concentration in the brain increased in synaptic membrane and synaptic vesicles and decreased in nuclei and cytosol as compared with the high dose. These results show that although the tissue concentration-time courses of anticholinergic drugs appear to decrease simply in parallel to plasma concentration, the subcellular distribution exhibits a variety of patterns among various tissues.|The pharmacokinetics of biperiden were studied and compared with pharmacodynamics (pupil size, accommodation, self-rating mood scale) in 6 healthy volunteers. A single-blind cross-over design was employed with placebo and biperiden (4 mg as commercially available tablets). After a lag time of 0.5 hr, biperiden was rapidly absorbed with a half-life of 0.3 hr, plasma peak levels of 5 ng/mL being reached after 1.5 hr. Biperiden showed good tissue penetration (distribution half-life 0.6 hr; ratio of total to central distribution volume 9.6), the terminal half-life time of plasma concentration was 18 hr, and the oral clearance was 146 L/hr. The pharmacodynamic maximum lagged behind the plasma peak concentration by 1 (self-rating) to 4 hr (accommodation).

The metabolism of biperiden is not completely understood, but does involve hydroxylation.

A single-blind cross-over design was employed with placebo and biperiden (4 mg as commercially available tablets). After a lag time of 0.5 hr, biperiden was rapidly absorbed with a half-life of 0.3 hr, ... Biperiden showed good tissue penetration (distribution half-life 0.6 hr; ratio of total to central distribution volume 9.6), the terminal half-life time of plasma concentration was 18 hr, ... .

Parkinsonism is thought to result from an imbalance between the excitatory (cholinergic) and inhibitory (dopaminergic) systems in the corpus striatum. The mechanism of action of centrally active anticholinergic drugs such as biperiden is considered to relate to competitive antagonism of acetylcholine at cholinergic receptors in the corpus striatum, which then restores the balance.|Akineton is a weak peripheral anticholinergic agent. It has, therefore, some antisecretory, antispasmodic and mydriatic effects. In addition, Akineton possesses nicotinolytic activity. Parkinsonism is thought to result from an imbalance between the excitatory (cholinergic) and inhibitory (dopaminergic) systems in the corpus striatum. The mechanism of action of centrally active anticholinergic drugs such as Akineton is considered to relate to competitive antagonism of acetylcholine at cholinergic receptors in the corpus striatum, which then restores the balance.|Like other antimuscarinic agents of the trihexyphenidyl group, biperiden has an atropine-like blocking action on parasympathetic-innervated peripheral structures, including smooth muscle. In addition to antispasmodic, antisecretory, and mydriatic effects, biperiden has an antinicotinic potency about 6 times that of atropine and 5 times that of trihexyphenidyl on a weight basis in experimental animals.

(1RS)-1-[(1SR,2SR,4SR)-bicyclo[2.2.1]hept-5-en-2-yl]-1-phenyl-3-(piperidin-1-yl)propan-1-ol (endo form); (1RS)-1-[(1SR,2RS,4SR)-bicyclo[2.2.1]hept-5-en-2-yl]-1-phenyl-3-(piperidin-1-yl)propan-1-ol; (1RS)-1-[(1RS,2RS,4RS)-bicyclo[2.2.1]hept-5-en-2-yl]-1-phenyl-3-(piperidin-1-yl)propan-1-ol; 1-[(1RS,2SR,4RS)-bicyclo[2.2.1]hept-5-en-2-yl]-3-(piperidin-1-yl)propan-1-one; 1-[(1RS,2RS,4RS)-bicyclo[2.2.1]hept-5-en-2-yl]-3-(piperidin-1-yl)propan-1-one; benzene

Emergency and supportive measures: Maintain an open airway and assist ventilation if needed. Treat hyperthermia, coma, rhabdomyolysis, and seizures if they occur. /Anticholinergics/|Specific drugs and antidotes: A small dose of physostigmine .... can be given to patients with severe toxicity (e.g., hyperthermia, severe delirium, or tachycardia). Caution: Physostigmine can cause AV block, asystole, and seizures, especially in patients with tricyclic antidepressant overdose. Neostigmine, a peripherally acting cholinesterase inhibitor, may be useful in treating anticholinergic-induced ileus. /Anticholinergics/|Decontamination: Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. Because of slowed gastrointestinal motility, gut decontamination procedures may be helpful even in late-presenting patients. /Anticholinergics/|Enhanced elimination: Hemodialysis, hemoperfusion, peritoneal dialysis, and repeat-dose charcoal are not effective in removing anticholinergic agents. /Anticholinergics/|For more Antidote and Emergency Treatment (Complete) data for BIPERIDEN (8 total), please visit the HSDB record page.

/SIGNS AND SYMPTOMS/ Overdosage with Akineton produces typical central symptoms of atropine intoxication (the central anticholinergic syndrome). Correct diagnosis depends upon recognition of the peripheral signs of parasympathetic blockade including dilated and sluggish pupils; warm, dry skin; facial flushing; decreased secretions of the mouth, pharynx, nose, and bronchi; foul-smelling breath; elevated temperature, tachycardia, cardiac arrhythmias, decreased bowel sounds, and urinary retention. Neuropsychiatric signs such as delirium, disorientation, anxiety, hallucinations, illusions, confusion, incoherence, agitation, hyperactivity, ataxia, loss of memory, paranoia, combativeness, and seizures may be present. The condition can progress to stupor, coma, paralysis, and cardiac and respiratory arrest and death.|/CASE REPORTS/ Two cases of self-induced intoxication with the anticholinergic agent biperiden (oral ingestion of at least 200 mg. in case 1, and of 60 mg. in combination with 300-400 mg levomepromazine in case 2) /were reported/. An acute delirious state and other somatic symptoms of a toxic anticholinergic action dominated the clinical picture. Serial measurements of biperiden serum levels revealed values up to 50-fold (case 1) and 15-fold (case 2) of those usually observed under therapeutic doses of biperiden. In both cases, the intoxication was controlled by the application of physostigmine and general therapeutic measures. ... The prognosis of biperiden intoxications, and the clinical symptomatology and therapy of drug-induced anticholinergic syndromes /is discussed/.|/CASE REPORTS/ Anticholinergic medication (ACM) is frequently used in psychiatry to treat the side-effects of D2 blocking agents. However, ACM is not without adverse effects and, in the elderly, cognitive and memory impairments have been emphasized. The aim of this study was to evaluate the effects of discontinuation of ACM on cognitive functions in a group of elderly chronic schizophrenia patients. Twenty-seven elderly patients (age 60 years or older), who were diagnosed as suffering from schizophrenia (DSM-IV) and receiving ACM in addition to antipsychotic treatment, were enrolled. Before and after ACM was discontinued, the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) subscale was administered. Twenty-one patients completed the study. All were receiving Akineton (biperiden), 2-6 mg daily before the study. Significant improvement in the ADAS-Cog total score was demonstrated (P < 0.03), as well as in the ideational praxia and orientation subscales. Improvement was correlated with the previous dose of biperidin. No adverse events or emergent extrapyramidal symptoms were noted. Discontinuation of ACM may be warranted in chronic schizophrenia patients since it may improve cognitive functioning with no adverse effects.|/CASE REPORTS/ A case of contact dermatitis to biperiden, an anti-Parkinson agent, and photocontact dermatitis to phenothiazines in a pharmacist was reported. The patient developed eczematous lesions on exposed area after she had worked at a psychiatric hospital for 6 months. She showed positive patch test reaction to biperiden. In addition, she reacted positively to photopatch testing with ultraviolet A and phenothiazines such as chlorpromazine and perphenazine.

Akineton

Oral: Tablets: 2 mg Akineton (scored) (Abbott). /Biperiden hydrochloride/

Analyte: biperidin; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: biperidin; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards|Analyte: biperidin; matrix: chemical identification; procedure: dissolution in phosphoric acid; production of a green color|Analyte: biperidin; matrix: chemical identification; procedure: dissolution in water and hydrochloric acid; addition of hydrochloric acid and mercuric chloride; formation of a white precipitate; or addition of bromine and formation of a yellow precipitate|For more Analytic Laboratory Methods (Complete) data for BIPERIDEN (18 total), please visit the HSDB record page.

Analyte: biperidin; matrix: blood (plasma); procedure: high-performance liquid chromatography with ultraviolet detection at 199 nm|Analyte: biperidin; matrix: blood (whole); procedure: high-performance liquid chromatography with ultraviolet detection at 200.5 nm

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals