T3DB: Biperiden

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (5)XML

Targets (5)

Record Information

Version

2.0

Creation Date

2009-07-21 20:27:42 UTC

Update Date

2014-12-24 20:25:53 UTC

Accession Number

T3D2897

Identification

Common Name

Biperiden

Class

Small Molecule

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]

Compound Type

Amine
Antidyskinetic
Antiparkinson Agent
Drug
Metabolite
Muscarinic Antagonist
Organic Compound
Parasympatholytic
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
1-Bicyclo[2.2.1]hept-5-en-2-yl-1-phenyl-3-piperidin-1-yl-propan-1-ol
Akineton
alpha-5-Norbornen-2-yl-alpha-phenyl-1-piperidinepropanol
alpha-Bicyclo[2.2.1]hept-5-en-2-yl-alpha-phenyl-1-piperidinepropanol
Beperiden
Bilino
Biperidene
Biperideno
Biperidenum
Biperidine
Ipsatol

Chemical Formula

C₂₁H₂₉NO

Average Molecular Mass

311.461 g/mol

Monoisotopic Mass

311.225 g/mol

CAS Registry Number

514-65-8

IUPAC Name

1-{bicyclo[2.2.1]hept-5-en-2-yl}-1-phenyl-3-(piperidin-1-yl)propan-1-ol

Traditional Name

biperiden

SMILES

OC(CCN1CCCCC1)(C1CC2CC1C=C2)C1=CC=CC=C1

InChI Identifier

InChI=1/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

InChI Key

InChIKey=YSXKPIUOCJLQIE-UHFFFAOYNA-N

Chemical Taxonomy

Description

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

Substituents

Aralkylamine
Monocyclic benzene moiety
Piperidine
Benzenoid
1,3-aminoalcohol
Tertiary alcohol
Tertiary amine
Tertiary aliphatic amine
Azacycle
Organoheterocyclic compound
Alcohol
Organic oxygen compound
Hydrocarbon derivative
Organooxygen compound
Organopnictogen compound
Aromatic alcohol
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

piperidines (CHEBI:3112 )
tertiary alcohol (CHEBI:3112 )
tertiary amino compound (CHEBI:3112 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	114°C
Boiling Point	Not Available
Solubility	25.1 mg/L
LogP	4.25

Predicted Properties

Property	Value	Source
Water Solubility	0.0043 g/L	ALOGPS
logP	4.28	ALOGPS
logP	3.54	ChemAxon
logS	-4.9	ALOGPS
pKa (Strongest Acidic)	13.82	ChemAxon
pKa (Strongest Basic)	9.3	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	23.47 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	97.02 m³·mol⁻¹	ChemAxon
Polarizability	36.74 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-0096-9261000000-a2bf53b32ad045169c69	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-054n-9520000000-3d69a8227dbbcbaa85a2	2017-11-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-01ox-1096000000-b99cc35f37f276338977	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0002-9040000000-0e1cce5acf474b6a379f	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-016r-9110000000-6c95e29e42a503874c09	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03di-0019000000-15b9d0ad97ade514831c	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-03ec-9145000000-6475a16f5449091aedb6	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-001i-9000000000-7c0cf15c2c8f5071caf7	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03di-4009000000-5d4593f5bf86b7105063	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0002-9002000000-91d2484c2b5c788ee347	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0002-9220000000-bd998e4698c9aaf6a99e	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03di-0009000000-db992041ed33362f9a42	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-03di-1549000000-050f3e90417671bee316	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a4i-1935000000-317f7afd162e7d4dca0b	2021-10-11	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0002-9000000000-92eb93b999cf7f5ec519	2014-09-20	View Spectrum

Toxicity Profile

Route of Exposure

Oral

Mechanism of Toxicity

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.

Metabolism

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

Toxicity Values

LD₅₀=760 mg/kg (Orally in rats).

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

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

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

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.

Treatment

Treatment of acute overdose revolves around symptomatic and supportive therapy. If Biperiden was administered orally, gastric lavage or other measures 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-base balance maintained. Urinary catheterization may be necessary. Routine use of physostigmine for overdose is controversial. Delirium, hallucinations, coma, and supraventricular tachycardia (not ventricular tachycardias or conduction defects) seem to respond. If indicated, 1 mg (half this amount for the children or elderly) may be given intramuscularly or by slow intravenous infusion. If there is no response within 20 minutes, and additional 1 mg dose may be given; this may be repeated until a total of 4 mg has been administered, a reversal of the toxic effects occur or excessive cholinergic signs are seen. Frequent monitoring of clinical signs should be done. Since physostigmine is rapidly destroyed, additional injections may be required every one or two hours to maintain control. The relapse intervals tend to lengthen as the toxic anticholinergic agent is metabolized, so the patient should be carefully observed for 8 to 12 hours following the last relapse. (3)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

3112

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Biperiden

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Biperiden

References

Synthesis Reference

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

MSDS

T3D2897.pdf

General References

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. [8420174 ]
Drugs.com [Link]
RxList: The Internet Drug Index (2009). [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Muscarinic acetylcholine receptor M1

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 action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:: CHRM1
Uniprot ID:: P11229
Molecular Weight:: 51420.375 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.00048 uM	Not Available	BindingDB 50240680

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
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. [17016423 ]
Bolden C, Cusack B, Richelson E: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther. 1992 Feb;260(2):576-80. [1346637 ]

Target Details

2. Neuronal acetylcholine receptor subunit alpha-2

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
Molecular Weight:: 59764.82 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
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. [17016423 ]

Target Details

3. Muscarinic acetylcholine receptor M2

General Function:: G-protein coupled acetylcholine receptor 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 action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
Gene Name:: CHRM2
Uniprot ID:: P08172
Molecular Weight:: 51714.605 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.0063 uM	Not Available	BindingDB 50240680

References

Bolden C, Cusack B, Richelson E: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther. 1992 Feb;260(2):576-80. [1346637 ]

Target Details

4. Muscarinic acetylcholine receptor M3

General Function:: Receptor 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 action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:: CHRM3
Uniprot ID:: P20309
Molecular Weight:: 66127.445 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.0039 uM	Not Available	BindingDB 50240680

References

Bolden C, Cusack B, Richelson E: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther. 1992 Feb;260(2):576-80. [1346637 ]

Target Details

5. Muscarinic acetylcholine receptor M4

General Function:: Guanyl-nucleotide exchange factor 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 action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
Gene Name:: CHRM4
Uniprot ID:: P08173
Molecular Weight:: 53048.65 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.0024 uM	Not Available	BindingDB 50240680

References

Bolden C, Cusack B, Richelson E: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther. 1992 Feb;260(2):576-80. [1346637 ]

Biperiden (T3D2897)

Structure for T3D2897: Biperiden

Targets

Binding/Activity Constants

References

References

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References