BIPERIDEN LACTATE

Details

Stereochemistry	UNKNOWN
Molecular Formula	C21H29NO.C3H6O3
Molecular Weight	401.539
Optical Activity	UNSPECIFIED
Defined Stereocenters	0 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(O)C(O)=O.OC(CCN1CCCCC1)(C2CC3CC2C=C3)C4=CC=CC=C4

InChI

InChIKey=GLPUBCPQWZZFNJ-UHFFFAOYSA-N

InChI=1S/C21H29NO.C3H6O3/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;1-2(4)3(5)6/h1,3-4,7-10,17-18,20,23H,2,5-6,11-16H2;2,4H,1H3,(H,5,6)

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 169 Target ID: CHEMBL216 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9798802	Antagonist 2778

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 8429	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 8429	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 8429	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 Co-administed with:: valpromide(15g, PO, single) alprazolam(20mg, PO, single) Sources: https://link.springer.com/article/10.2165/00128415-201013120-00042	unhealthy, 35 n = 1 Health Status: unhealthy Condition: bipolar disorder Age Group: 35 Sex: F Population Size: 1 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) n = 9 Health Status: unhealthy Condition: depression Age Group: 44 (29-55) Sex: M+F Population Size: 9 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 Co-administed with:: valpromide(15g, PO, single) alprazolam(20mg, PO, single) Sources: https://link.springer.com/article/10.2165/00128415-201013120-00042	unhealthy, 35 n = 1 Health Status: unhealthy Condition: bipolar disorder Age Group: 35 Sex: F Population Size: 1 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 Co-administed with:: valpromide(15g, PO, single) alprazolam(20mg, PO, single) Sources: https://link.springer.com/article/10.2165/00128415-201013120-00042	unhealthy, 35 n = 1 Health Status: unhealthy Condition: bipolar disorder Age Group: 35 Sex: F Population Size: 1 Sources: https://link.springer.com/article/10.2165/00128415-201013120-00042

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 activator 80 substrate 1737		inhibitor 1852 substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461	P-gp 1537 CYP1A2 1054

Drug as perpetrator

Target	Modality	Activity
P-gp 1650	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw0MzAyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExMDEifX0%3D	no
CYP3A4 1925	activator 214 Sources: https://link.springer.com/article/10.1007%2Fs002280050455	weak [Activation 0.1 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://link.springer.com/article/10.1007%2Fs002280050455	yes [Inhibition 100 uM]
CYP2D6 1891	inhibitor 3277 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 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22554863/, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw0MzAyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExMDEifX0%3D	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9342584/, https://www.tandfonline.com/doi/abs/10.1080/03602530903118729	yes [Km 37 uM]
CYP1A2 1054	substrate 3367 Sources: https://www.tandfonline.com/doi/abs/10.1080/03602530903118729	yes
CYP3A4 1737	substrate 3367 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
BLD Pharm	BD116739	http://www.bldpharm.com/products/514-65-8.html
BioCrick	BCC4274	http://www.biocrick.com/Biperiden-BCC4274.html
CSNpharm	CSN10453	https://www.csnpharm.com/products/biperiden.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
DC Chemicals	DC23078	http://www.dcchemicals.com/product_show-DC23078.html
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
eNovation Chemicals	D383306	http://www.enovationchem.com/productDetails.asp?productID=D383306

PubMed

Title	Date	PubMed
Tardive dystonia induced by risperidone.	1999 Jun	10389620
Quantitative prediction of catalepsy induced by amoxapine, cinnarizine and cyclophosphamide in mice.	2000 May	11180191
Effects of advanced candidate anticonvulsants under two rodent models of 'counting'.	2001 Dec	11920930
Combination anticonvulsant treatment of soman-induced seizures.	2001 Dec	11920921
A case of child abuse: haloperidol poisoning of a child caused by his mother.	2001 Dec	11785601
Effects of olanzapine and other antipsychotics on cognitive function in chronic schizophrenia: a longitudinal study.	2001 Mar 1	11278151
A case of Parkinsonism due to lithium intoxication: treatment with Pramipexole.	2002 May	12093142
Tardive dyskinesia with risperidone and anticholinergics.	2002 Nov	12411240
Effects of anticholinergics on serial-probe recognition accuracy of rhesus macaques (Macaca mulatta).	2002 Nov	12213528
Effect of sabcomeline on muscarinic and dopamine receptor binding in intact mouse brain.	2003 Apr	12790361
A CYP2D6 phenotype-genotype mismatch in Japanese psychiatric patients.	2003 Sep	14571354
Acute dystonia caused by low dosage of olanzapine.	2003 Spring	12724469
Antiparkinsonian-like effects of Plumbago scandens on tremorine-induced tremors methodology.	2004 Dec	15582683
Effects of discontinuation of long-term anticholinergic treatment in elderly schizophrenia patients.	2004 Jan	15101567
Use of polypharmacotherapy in pregnancy: a prospective outcome in a case.	2004 May	15093969
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
Beneficial antipsychotic effects of allopurinol as add-on therapy for schizophrenia: a double blind, randomized and placebo controlled trial.	2005 Feb	15694232
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
Evaluation of the clinical efficacy of risperidone for untreated and treated cases of schizophrenia from various aspects.	2005 Oct	16194258
Measurement of anticholinergic effects of psychotropic drugs in humans.	2005 Sep	16189744
Modification of practice-dependent plasticity in human motor cortex by neuromodulators.	2006 Aug	16221926
[The prevalence and pharmacological cost of Parkinson's disease in Spain].	2006 Dec 1-15	17133323
[Therapy of postoperative nausea and vomiting in ENT--tardive dyskinesia as an adverse effect of metoclopramid--a case report].	2006 Nov	16586284
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
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 LACTATE

Common Name

English

1-PIPERIDINEPROPANOL, .ALPHA.-BICYCLO(2.2.1)HEPT-5-EN-2-YL-.ALPHA.-PHENYL-, COMPD. WITH 2-HYDROXYPROPANOIC ACID (1:1)

Systematic Name

English

BIPERIDEN LACTATE [MART.]

Common Name

English

BIPERIDEN LACTATE [USP IMPURITY]

Common Name

English

α-5-Norbornen-2-yl-α-phenyl-1-piperidinepropanol lactate (salt)

Common Name

English

BIPERIDEN LACTATE [ORANGE BOOK]

Common Name

English

Biperiden lactate [WHO-DD]

Common Name

English

BIPERIDEN LACTATE [VANDF]

Common Name

English

BIPERIDEN LACTATE [JAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29704