BIPERIDEN

Details

Stereochemistry	UNKNOWN
Molecular Formula	C21H29NO
Molecular Weight	311.4611
Optical Activity	UNSPECIFIED
Defined Stereocenters	0 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(CCN1CCCCC1)(C2CC3CC2C=C3)C4=CC=CC=C4

InChI

InChIKey=YSXKPIUOCJLQIE-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Description
Sources: https://mri.cts-mrp.eu/Human/Downloads/AT_H_0521_002_FinalSPC.pdf
Curator's Comment: description was created based on several sources, including https://www.tga.gov.au/alert/akineton-biperiden-hydrochloride-2-mg-tablets https://www.drugs.com/pro/akineton.html

Biperiden, sold under the brandname Akineton was used as an adjunct in the therapy of all forms of parkinsonism (postencephalitic, arteriosclerotic and idiopathic). Was also useful in the control of extrapyramidal disorders due to central nervous system drugs such as phenothiazines and other groups of psychotropics. Biperiden is a weak peripheral anticholinergic agent. It has, therefore, some antisecretory, antispasmodic and mydriatic effects. In addition, biperiden 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 biperiden is considered to relate to competitive antagonism of acetylcholine at cholinergic receptors in the corpus striatum, which then restores the balance. Atropine-like side effects such as dry mouth; blurred vision; drowsiness; euphoria or disorientation; urinary retention; postural hypotension; constipation; agitation; disturbed behavior may been seen. Only limited pharmacokinetic studies of biperiden in humans are available.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Muscarinic acetylcholine receptor M1 168 Target ID: CHEMBL216 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9798802	Antagonist 2849

Conditions

Condition	Modality	Highest Phase	Product
Postencephalitic parkinsonism 7 Sources: https://mri.cts-mrp.eu/Human/Downloads/AT_H_0521_002_FinalSPC.pdf https://www.ncbi.nlm.nih.gov/pubmed/14393477 http://www.clinicaladvisor.com/akineton/drug/3903/	Palliative	Approved 8583	AKINETON Approved Use For use as an adjunct in the therapy of all forms of parkinsonism (postencephalitic, arteriosclerotic and idiopathic). Useful in the control of extrapyramidal disorders due to central nervous system drugs such as phenothiazines and other groups of psychotropics. Launch Date 1959
Idiopathic Parkinson's disease 19 Sources: https://mri.cts-mrp.eu/Human/Downloads/AT_H_0521_002_FinalSPC.pdf http://www.clinicaladvisor.com/akineton/drug/3903/	Palliative	Approved 8583	AKINETON Approved Use For use as an adjunct in the therapy of all forms of parkinsonism (postencephalitic, arteriosclerotic and idiopathic). Useful in the control of extrapyramidal disorders due to central nervous system drugs such as phenothiazines and other groups of psychotropics. Launch Date 1959
Arteriosclerotic parkinsonism 5 Sources: https://mri.cts-mrp.eu/Human/Downloads/AT_H_0521_002_FinalSPC.pdf http://www.clinicaladvisor.com/akineton/drug/3903/	Palliative	Approved 8583	AKINETON Approved Use For use as an adjunct in the therapy of all forms of parkinsonism (postencephalitic, arteriosclerotic and idiopathic). Useful in the control of extrapyramidal disorders due to central nervous system drugs such as phenothiazines and other groups of psychotropics. Launch Date 1959

C_max

Value	Dose	Co-administered	Analyte	Population
13.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3709619/	4 mg single, intravenous dose: 4 mg route of administration: Intravenous experiment type: SINGLE co-administered:		BIPERIDEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
62.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3709619/	4 mg single, intravenous dose: 4 mg route of administration: Intravenous experiment type: SINGLE co-administered:		BIPERIDEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
24.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3709619/	4 mg single, intravenous dose: 4 mg route of administration: Intravenous experiment type: SINGLE co-administered:		BIPERIDEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
600 mg 1 times / day single, oral Overdose Dose: 600 mg, 1 times / day Route: oral Route: single Dose: 600 mg, 1 times / day Sources: https://link.springer.com/article/10.2165/00128415-201013120-00042	unhealthy, 35 Health Status: unhealthy Age Group: 35 Sex: F Sources: https://link.springer.com/article/10.2165/00128415-201013120-00042	Other AEs: Hallucinations, Coma... Other AEs: Hallucinations Coma Sources: https://link.springer.com/article/10.2165/00128415-201013120-00042
4 mg 3 times / day multiple, oral Highest studied dose Dose: 4 mg, 3 times / day Route: oral Route: multiple Dose: 4 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8570773/	unhealthy, 44 (29-55) Health Status: unhealthy Age Group: 44 (29-55) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/8570773/	Sources: https://pubmed.ncbi.nlm.nih.gov/8570773/

AEs

AE	Significance	Dose	Population
Coma		600 mg 1 times / day single, oral Overdose Dose: 600 mg, 1 times / day Route: oral Route: single Dose: 600 mg, 1 times / day Sources: https://link.springer.com/article/10.2165/00128415-201013120-00042	unhealthy, 35 Health Status: unhealthy Age Group: 35 Sex: F Sources: https://link.springer.com/article/10.2165/00128415-201013120-00042
Hallucinations		600 mg 1 times / day single, oral Overdose Dose: 600 mg, 1 times / day Route: oral Route: single Dose: 600 mg, 1 times / day Sources: https://link.springer.com/article/10.2165/00128415-201013120-00042	unhealthy, 35 Health Status: unhealthy Age Group: 35 Sex: F Sources: https://link.springer.com/article/10.2165/00128415-201013120-00042

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 activator 150 substrate 1946		inhibitor 2507 substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741	P-gp 2052 CYP1A2 1197

Drug as perpetrator

Target	Modality	Activity
P-gp 1932	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw0MzAyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExMDEifX0%3D	no
CYP3A4 2633	activator 342 Sources: https://link.springer.com/article/10.1007%2Fs002280050455	weak [Activation 0.1 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://link.springer.com/article/10.1007%2Fs002280050455	yes [Inhibition 100 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://go.drugbank.com/drugs/DB00810, https://link.springer.com/article/10.1007%2Fs002280050322, https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000514658	yes [Ki 0.45 uM]

Drug as victim

Target	Modality	Activity
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/22554863/, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw0MzAyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExMDEifX0%3D	no
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9342584/, https://www.tandfonline.com/doi/abs/10.1080/03602530903118729	yes [Km 37 uM]
CYP1A2 1197	substrate 4014 Sources: https://www.tandfonline.com/doi/abs/10.1080/03602530903118729	yes
CYP3A4 1946	substrate 4014 Sources: https://www.tandfonline.com/doi/abs/10.1080/03602530903118729	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY445564	https://www.001chemical.com/chem/514-65-8
Ambinter	Amb10843814	http://www.ambinter.com/reference/10843814
BioCrick	BCC4274	http://www.biocrick.com/Biperiden-BCC4274.html
BLD Pharm	BD116739	http://www.bldpharm.com/products/514-65-8.html
Chem Scene	CS-1797	http://www.chemscene.com/514-65-8.html
ChemMol	49427588	http://www.chemmol.com/chemmol/49427588.html
Chemspace	CSSB00020627468	https://chem-space.com/CSSB00020627468
CSNpharm	CSN10453	https://www.csnpharm.com/products/biperiden.html
DC Chemicals	DC23078	http://www.dcchemicals.com/product_show-DC23078.html
eNovation Chemicals	D383306	http://www.enovationchem.com/productDetails.asp?productID=D383306
Lab Network	LN01267554	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01267554
MedChem Express	HY-13204A	https://www.medchemexpress.com/Biperiden.html
Molcore	MC445564	https://www.molcore.com/product/514-65-8
MuseChem	I003854	https://www.musechem.com/product/I003854.html
Parchem	28356	http://www.parchem.com/chemical-supplier-distributor/Biperiden-018356.aspx
Smolecule	S521354	http://www.smolecule.com/products/s521354
THE BioTek	bt-262503	https://www.thebiotek.com/product/inhibitors/bt-262503
Vesino Industrial Co Ltd	VA10409	http://www.vsnchem.com/goto/product/23881/
Vitas-M Laboratory	STL582281	http://www.request.vitasmlab.biz/index.php?option=com_search_stk&Itemid=22&stk=STL582281&?utm_source=pubchem&utm_medium=p_search_link&utm_campaign=pubchem_search&utm_content=pubchem_slink
Yuhao Chemical	HL1932	http://www.chemyuhao.com/514-65-8.html

PubMed

Title	Date	PubMed
[Treatment of the neuroleptic syndrome by biperiden hydrochloride under its delayed-action form. A 9-month study on 55 hospitalized patients].	1976	1001242
[Effect of diazepam on the effectiveness of antidote therapy in eliminating the acute lethal effects of soman in mice].	2001 Aug	11678028
A case of child abuse: haloperidol poisoning of a child caused by his mother.	2001 Dec	11785601
The influence of pilocarpine and biperiden on pH value and calcium, phosphate, and bicarbonate concentrations in saliva during and after radiotherapy for head and neck cancer.	2001 Nov	11709686
Simultaneous determination of enantiomers of structurally related anticholinergic analogs in human serum by liquid chromatography-electrospray ionization mass spectrometry with on-line sample cleanup.	2001 Oct 25	11678378
Motor disturbances in mice with deficiency of the sodium channel gene Scn8a show features of human dystonia.	2003 Dec	14769375
In vitro drug-drug interactions with perospirone and concomitantly administered drugs in human liver microsomes.	2003 Jan-Mar	14503667
Influences of an anticholinergic antiparkinsonian drug, parkinsonism, and psychotic symptoms on cardiac autonomic function in schizophrenia.	2003 Oct	14520119
Antiparkinsonian-like effects of Plumbago scandens on tremorine-induced tremors methodology.	2004 Dec	15582683
Pharmacological modulation of cholinergic brain activity and its reflection in special EEG frequency ranges from various brain areas in the freely moving rat (Tele-Stereo-EEG).	2005 Dec	16009538
Major depressive disorder with psychotic features induced by interferon-alpha treatment for hepatitis C in a polydrug abuser.	2005 Jan	15671136
Possible malignant neuroleptic syndrome that associated with hypothyroidism.	2005 Jun	15927337
Alterations in behavioral responses to a cholinergic agonist in post-pubertal rats with neonatal ventral hippocampal lesions: relationship to changes in muscarinic receptor levels.	2005 Jun	15637638
The effects of amisulpride on five dimensions of psychopathology in patients with schizophrenia: a prospective open-label study.	2005 May 3	15869707
Modulation of memory and visuospatial processes by biperiden and rivastigmine in elderly healthy subjects.	2005 Sep	16041534
[The prevalence and pharmacological cost of Parkinson's disease in Spain].	2006 Dec 1-15	17133323
Neuroleptic malignant syndrome induced by ziprasidone on the second day of treatment.	2007	17366349
Acute dystonia resulting from abrupt bupropion discontinuation.	2007 Apr 13	17218049
Early onset of treatment effects with oral risperidone.	2007 Jan 19	17239237
Simultaneous prescribing of atypical antipsychotics, conventional antipsychotics and anticholinergics-a European study.	2007 Jun	17333501

Patents

Sample Use Guides

In Vivo Use Guide

Parkinsonism: Dosage should be individualized. Begin with 1/2 a tablet twice daily, and gradually increase to 1 tablet, 3-4 times daily.

Route of Administration: Oral

In Vitro Use Guide

(+)-Biperiden had its highest affinity to M1-receptors (pA2 = 9.07), had low affinity to cardiac M2 alpha-receptors (pA2 = 7.25) and intermediate affinity to ileal M2 beta-receptors (pA2 = 8.27). The ability of (+)-biperiden to discriminate between ileal M2 beta- and cardiac M2 alpha-receptors (factor = 10) was similar to that of 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, factor = 9). In contrast, (-)-biperiden displayed low but nearly undistinguishable affinity for all muscarinic receptor subtypes studied (pA2 = 5.59 +/- 6.38). (+)-Biperiden discriminated strongly between M1- and cardiac M2 alpha-receptors (factor 66), thus being even more selective than pirenzepine (factor 28) which makes it one of the most M1-/cardiac M2 alpha-selective antimuscarinic drugs now available.

Name

Type

Language

BIPERIDEN

Official Name

English

KL 373

Preferred Name

English

NSC-759145

Code

English

BIPERIDEN [MART.]

Common Name

English

?-5-Norbornen-2-yl-?-phenyl-1-piperidinepropanol

Systematic Name

English

BIPERIDEN [JAN]

Common Name

English

BIPERIDEN [USP IMPURITY]

Common Name

English

BIPERIDEN [HSDB]

Common Name

English

BIPERIDEN [WHO-IP]

Common Name

English

BIPERIDENUM [WHO-IP LATIN]

Common Name

English

BIPERIDEN [MI]

Common Name

English

BIPERIDEN [VANDF]

Common Name

English

biperiden [INN]

Common Name

English

AKINETON-

Common Name

English

1-PIPERIDINEPROPANOL, .ALPHA.-BICYCLO(2.2.1)HEPT-5-EN-2-YL-.ALPHA.-PHENYL-

Systematic Name

English

Biperiden [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

N04AA02