FENDILINE HYDROCHLORIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C23H25N.ClH
Molecular Weight	351.912
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CC(NCCC(C1=CC=CC=C1)C2=CC=CC=C2)C3=CC=CC=C3

InChI

InChIKey=NJXWZWXCHBNOOG-UHFFFAOYSA-N

InChI=1S/C23H25N.ClH/c1-19(20-11-5-2-6-12-20)24-18-17-23(21-13-7-3-8-14-21)22-15-9-4-10-16-22;/h2-16,19,23-24H,17-18H2,1H3;1H

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3310016 | https://www.ncbi.nlm.nih.gov/pubmed/23129805

Fendiline or Sensit (N-(3,3-diphenylpropyl)-(1-phenylethyl)-amine), is a diphenylalkylamine blocker of L-type calcium channels. Fendiline is an anti-anginal agent for the treatment of coronary heart disease. Pharmaco-dynamically, it exerts the typical calcium as well as calmodulin antagonistic actions: inhibition of the transmembrane calcium current, smooth muscle relaxation, negative inotropism, cardioprotection, inhibition of calmodulin-activated myosin light-chain kinase and phosphodiesterase. Pharmacokinetics reveal slow onset of action and a long half-life. The anti-anginal and anti-ischaemic efficacy of fendiline has been proven in several placebo-controlled, double-blind trials. Fendiline is an FDA-approved, albeit now clinically obsolete. Additionally, fendiline is a specific inhibitor of K-Ras plasma membrane localization that also inhibits K-Ras signal output and blocks the proliferation of K-Ras-transformed tumor cells.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-gated L-type calcium channel 95 Target ID: CHEMBL2095229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8485628 \| https://www.ncbi.nlm.nih.gov/pubmed/9580596	Blocker 555		17.0 µM [IC50]
GTPase KRas 5 Target ID: CHEMBL2189121 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23129805	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Angina pectoris 110 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7188139 https://www.ncbi.nlm.nih.gov/pubmed/3449975 https://www.ncbi.nlm.nih.gov/pubmed/1764956 https://www.ncbi.nlm.nih.gov/pubmed/3310016	Primary	Approved 8583	Sensit Approved Use Unknown
Anxiety 275 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9162271	Primary	Preclinical	Unknown Approved Use Unknown
Drug addiction 5 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24264565 https://www.ncbi.nlm.nih.gov/pubmed/26345344	Primary	Preclinical	Unknown Approved Use Unknown
Cancer 609 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23129805	Primary	Basic research	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
4.2 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7117293/	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	FENDILINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
7.2 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7117293/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	FENDILINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
8.8 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7117293/	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:	FENDILINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
39.8 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7117293/	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	FENDILINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
111.2 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7117293/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	FENDILINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
219.6 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7117293/	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:	FENDILINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
20 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/3566858/	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	FENDILINE plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
19.4 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7117293/	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	FENDILINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
22 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7117293/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	FENDILINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
35.6 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7117293/	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:	FENDILINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1200 mg single, oral Highest studied dose Dose: 1200 mg Route: oral Route: single Dose: 1200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3566858/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/3566858/	Sources: https://pubmed.ncbi.nlm.nih.gov/3566858/
400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3566858/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/3566858/	Disc. AE: Trembling, Dizziness... AEs leading to discontinuation/dose reduction: Trembling Dizziness Sources: https://pubmed.ncbi.nlm.nih.gov/3566858/

AEs

AE	Significance	Dose	Population
Dizziness	Disc. AE	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3566858/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/3566858/
Trembling	Disc. AE	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3566858/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/3566858/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 1079 OATP2B1 157 OATP1B3 961 MRP2 499

Drug as perpetrator

Target	Modality	Activity
OATP1B1 1095	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	no [Inhibition 20 uM]
OATP1B3 970	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	no [Inhibition 20 uM]
OATP2B1 162	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	no [Inhibition 20 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/3336#section=Biological-Test-Results Page: 1.0	yes [IC50 0.0871 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/3336#section=Biological-Test-Results Page: 7.0	yes [IC50 13.8029 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/3336#section=Biological-Test-Results Page: 6.0	yes [IC50 8.709 uM]
MRP2 625	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/18457386/	yes [Inhibition 80 uM]

PubMed

Title	Date	PubMed
LuxR-dependent quorum sensing: computer aided discovery of new inhibitors structurally unrelated to N-acylhomoserine lactones.	2010-08-01	20615699
Contractile actions of L-type Ca2+ agonists in human vas deferens and effects of structurally different Ca2+ antagonists.	2010-02-10	19878664
Fendiline-evoked [Ca2+]i rises and non-Ca2+-triggered cell death in human oral cancer cells.	2009-01	19411560
Interaction of antagonists with calmodulin: insights from molecular dynamics simulations.	2008-06-12	18459732
[Role of apoptosis in the kidney after reperfusion].	2008-02-17	18258561
Allosteric modulators of GABA(B) receptors: mechanism of action and therapeutic perspective.	2007-09	19305802
Allosteric modulation of the calcium-sensing receptor.	2007-09	19305800
2'-hydroxy-fendiline analogues as potent relaxers of isolated arteries.	2007-04-30	17331497
Quantitative structure-pharmacokinetic relationships for drug clearance by using statistical learning methods.	2006-03	16290201
Spectrofluorimetric determination of fendiline in tablets.	2005-10	16259131
GABA(B) receptor modulators potentiate baclofen-induced depression of dopamine neuron activity in the rat ventral tegmental area.	2005-04	15711597
3-Chloro,4-methoxyfendiline is a potent GABA(B) receptor potentiator in rat neocortical slices.	2005-01-10	15659292
Allosteric modulation of GABA(B) receptor function in human frontal cortex.	2005-01	15627515
Clinical potential of GABAB receptor modulators.	2005	16389296
Calcimimetic and calcilytic drugs: just for parathyroid cells?	2004-03	15200152
Calcium sensing receptors as integrators of multiple metabolic signals.	2004-03	15200144
Arylalkylamines are a novel class of positive allosteric modulators at GABA(B) receptors in rat neocortex.	2002-09-06	12223231
The anti-anginal drug fendiline elevates cytosolic Ca(2+) in rabbit corneal epithelial cells.	2002-07-19	12088766
Fendiline mobilizes intracellular Ca2+ in Chang liver cells.	2001-09	11553031
Effects of the antianginal drug fendiline on Ca2+ movement in hepatoma cells.	2001-07	11530834
Fendiline, an anti-anginal drug, increases intracellular Ca2+ in PC3 human prostate cancer cells.	2001-07	11488522
Determination of fendiline and gallopamil by capillary isotachophoresis.	2001-06-15	11417865
Dual effect of the antianginal drug fendiline on bladder female transitional carcinoma cells: mobilization of intracellular CA2+ and induction of cell death.	2001-05	11359998
Fendiline-Induced Ca2+ movement in A10 smooth muscle cells.	2001-03-31	11403516
The anti-anginal drug fendiline increases intracellular Ca(2+) levels in MG63 human osteosarcoma cells.	2001-03-08	11246176
Inhibitors of calmodulin impair the constitutive but not the inducible nitric oxide synthase activity in the rat aorta.	1992-05	1374468
Effects of the calmodulin antagonists fendiline and calmidazolium on aggregation, secretion of ATP, and internal calcium in washed human platelets.	1991-01	2030746

Patents

Sample Use Guides

In Vivo Use Guide

Pharmacokinetics in healthy volunteers: single doses of 200, 400, 600, 800, 1000, and 1200 mg; or 400 mg twice daily

Route of Administration: Oral

In Vitro Use Guide

Fendiline (100-200 microM) reduced the postsynaptic influx of calcium but did not alter calcium loss from the extracellular space into presynaptic terminals in the rat hippocampus in vitro.

Name

Type

Language

FENDILINE HYDROCHLORIDE

Common Name

English

CORDAN

Preferred Name

English

FENDILAR

Brand Name

English

SENSIT

Brand Name

English

BENZENEPROPANAMINE, .GAMMA.-PHENYL-N-(1-PHENYLETHYL)-, HYDROCHLORIDE (1:1)

Systematic Name

English

FENDILINE HYDROCHLORIDE [MART.]

Common Name

English

NSC-757826

Code

English

BENZYLAMINE, N-(3,3-DIPHENYLPROPYL)-.ALPHA.-METHYL-, HYDROCHLORIDE

Systematic Name

English

BENZENEPROPANAMINE, .GAMMA.-PHENYL-N-(1-PHENYLETHYL)-, HYDROCHLORIDE

Systematic Name

English

FENDILINE HYDROCHLORIDE [MI]

Common Name

English

Fendiline hydrochloride [WHO-DD]

Common Name

English

N-(2-BENZHYDRYLETHYL)-.ALPHA.-METHYLBENZYLAMINE HYDROCHLORIDE

Systematic Name

English

PHENOXAN

Brand Name

English

SENSITE

Brand Name

English

FENDILINE HCL

Common Name

English

Code System Code Type Description

SMS_ID

100000092346