Identification

Name
Biperiden
Accession Number
DB00810  (APRD00725)
Type
Small Molecule
Groups
Approved, Investigational
Description

A muscarinic antagonist that has effects in both the central and peripheral nervous systems. It has been used in the treatment of arteriosclerotic, idiopathic, and postencephalitic parkinsonism. It has also been used to alleviate extrapyramidal symptoms induced by phenothiazine derivatives and reserpine. [PubChem]

Structure
Thumb
Synonyms
  • 1-Bicyclo[2.2.1]hept-5-en-2-yl-1-phenyl-3-piperidin-1-yl-propan-1-ol
  • alpha-5-Norbornen-2-yl-alpha-phenyl-1-piperidinepropanol
  • alpha-Bicyclo[2.2.1]hept-5-en-2-yl-alpha-phenyl-1-piperidinepropanol
  • Beperiden
  • Biperiden
  • Biperidene
  • Biperideno
  • Biperidenum
Product Ingredients
IngredientUNIICASInChI Key
Biperiden hydrochlorideK35N76CUHF1235-82-1RDNLAULGBSQZMP-UHFFFAOYSA-N
Biperiden lactate09TD6C51477085-45-2GLPUBCPQWZZFNJ-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AkinetonTablet2 mg/1OralPar Pharmaceutical2004-12-122006-12-12Us
AkinetonTablet2 mg/1OralPhysicians Total Care, Inc.1996-06-102006-12-31Us
Akineton Tab 2mgTablet2 mgOralAbbott1985-12-312007-07-31Canada
International/Other Brands
Akineton (Abbott) / Bilino (Winston) / Ipsatol (Orion)
Categories
UNII
0FRP6G56LD
CAS number
514-65-8
Weight
Average: 311.4611
Monoisotopic: 311.224914555
Chemical Formula
C21H29NO
InChI Key
YSXKPIUOCJLQIE-UHFFFAOYSA-N
InChI
InChI=1S/C21H29NO/c23-21(19-7-3-1-4-8-19,11-14-22-12-5-2-6-13-22)20-16-17-9-10-18(20)15-17/h1,3-4,7-10,17-18,20,23H,2,5-6,11-16H2
IUPAC Name
1-{bicyclo[2.2.1]hept-5-en-2-yl}-1-phenyl-3-(piperidin-1-yl)propan-1-ol
SMILES
OC(CCN1CCCCC1)(C1CC2CC1C=C2)C1=CC=CC=C1

Pharmacology

Indication

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

Pharmacodynamics

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.

Mechanism of action

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.

TargetActionsOrganism
ANeuronal acetylcholine receptor subunit alpha-2
antagonist
Human
AMuscarinic acetylcholine receptor M1
antagonist
Human
Absorption

87% bioavailability

Volume of distribution
Not Available
Protein binding

60%

Metabolism

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

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

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.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Biperiden can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of Tachycardia can be increased when Biperiden is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of Tachycardia can be increased when Biperiden is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of Tachycardia can be increased when Biperiden is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of Tachycardia can be increased when Biperiden is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Biperiden.
AbediterolThe risk or severity of Tachycardia can be increased when Biperiden is combined with Abediterol.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Biperiden.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Biperiden.
AclidiniumThe risk or severity of adverse effects can be increased when Biperiden is combined with Aclidinium.
Food Interactions
  • Avoid alcohol.
  • Take with food.

References

Synthesis Reference

Peter Klein, "Method for the production of biperiden II." U.S. Patent US20040152899, issued August 05, 2004.

US20040152899
General References
  1. Nishiyama K, Mizuno T, Sakuta M, Kurisaki H: Chronic dementia in Parkinson's disease treated by anticholinergic agents. Neuropsychological and neuroradiological examination. Adv Neurol. 1993;60:479-83. [PubMed:8420174]
External Links
Human Metabolome Database
HMDB0014948
KEGG Drug
D00779
KEGG Compound
C07941
PubChem Compound
2381
PubChem Substance
46508325
ChemSpider
2289
BindingDB
50240680
ChEBI
3112
ChEMBL
CHEMBL1101
Therapeutic Targets Database
DAP001125
PharmGKB
PA448626
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Biperiden
ATC Codes
N04AA02 — Biperiden

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2, 3CompletedTreatmentCocaine Related Disorders1
3CompletedTreatmentCrack Cocaine Dependence / Dependence, Cocaine1
3RecruitingTreatmentTraumatic Brain Injury (TBI)1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
4Unknown StatusTreatmentDependence, Cocaine1

Pharmacoeconomics

Manufacturers
  • Abbott laboratories
Packagers
  • Abbott Laboratories Ltd.
  • BASF Corp.
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
TabletOral2 mg/1
TabletOral2 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)114 °CPhysProp
water solubility25.1 mg/LNot Available
logP4.25SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.00426 mg/mLALOGPS
logP4.28ALOGPS
logP3.54ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)13.82ChemAxon
pKa (Strongest Basic)9.3ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area23.47 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity97.02 m3·mol-1ChemAxon
Polarizability36.74 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9669
Blood Brain Barrier+0.9808
Caco-2 permeable+0.6422
P-glycoprotein substrateSubstrate0.7189
P-glycoprotein inhibitor IInhibitor0.6211
P-glycoprotein inhibitor IINon-inhibitor0.8284
Renal organic cation transporterInhibitor0.7592
CYP450 2C9 substrateNon-substrate0.8119
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5193
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9084
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9056
CYP450 3A4 inhibitorNon-inhibitor0.9041
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9558
Ames testNon AMES toxic0.8194
CarcinogenicityNon-carcinogens0.9309
BiodegradationNot ready biodegradable0.8756
Rat acute toxicity2.6495 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6982
hERG inhibition (predictor II)Non-inhibitor0.6332
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.72 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Mass Spectrum (Electron Ionization)MSsplash10-0002-9000000000-92eb93b999cf7f5ec519
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as aralkylamines. These are alkylamines in which the alkyl group is substituted at one carbon atom by an aromatic hydrocarbyl group.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Amines
Direct Parent
Aralkylamines
Alternative Parents
Piperidines / Benzene and substituted derivatives / Tertiary alcohols / 1,3-aminoalcohols / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives / Aromatic alcohols
Substituents
Aralkylamine / Monocyclic benzene moiety / Piperidine / Benzenoid / 1,3-aminoalcohol / Tertiary alcohol / Tertiary amine / Tertiary aliphatic amine / Azacycle / Organoheterocyclic compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
piperidines, tertiary alcohol, tertiary amino compound (CHEBI:3112)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Drug binding
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Gene Name
CHRNA2
Uniprot ID
Q15822
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-2
Molecular Weight
59764.82 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Hosoi R, Kobayashi K, Watanabe Y, Inoue O: Evaluation of in vivo binding properties of 3H-NMPB and 3H-QNB in mouse brain. J Neural Transm (Vienna). 1999;106(7-8):583-92. [PubMed:10907719]
  4. Pehl C, Wendl B, Kaess H, Pfeiffer A: Effects of two anticholinergic drugs, trospium chloride and biperiden, on motility and evoked potentials of the oesophagus. Aliment Pharmacol Ther. 1998 Oct;12(10):979-84. [PubMed:9798802]
  5. Eltze M: Multiple mechanisms of action: the pharmacological profile of budipine. J Neural Transm Suppl. 1999;56:83-105. [PubMed:10370904]
  6. Eltze M, Galvan M: Involvement of muscarinic M2 and M3, but not of M1 and M4 receptors in vagally stimulated contractions of rabbit bronchus/trachea. Pulm Pharmacol. 1994 Apr;7(2):109-20. [PubMed:8081071]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Kudo S, Uchida M, Odomi M: Metabolism of carteolol by cDNA-expressed human cytochrome P450. Eur J Clin Pharmacol. 1997;52(6):479-85. [PubMed:9342584]

Drug created on June 13, 2005 07:24 / Updated on December 14, 2018 12:39