FENDILINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C23H25N
Molecular Weight	315.4513
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=NMKSAYKQLCHXDK-UHFFFAOYSA-N

InChI=1S/C23H25N/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

HIDE SMILES / InChI

Molecular Formula	C23H25N
Molecular Weight	315.4513
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

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 92 Target ID: CHEMBL2095229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8485628 \| https://www.ncbi.nlm.nih.gov/pubmed/9580596	Blocker 537		17.0 µM [IC50]
GTPase KRas 3 Target ID: CHEMBL2189121 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23129805	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Angina pectoris 106 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 8429	Sensit Approved Use Unknown
Anxiety 267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9162271	Primary	Preclinical	Unknown Approved Use Unknown
Drug addiction 4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24264565 https://www.ncbi.nlm.nih.gov/pubmed/26345344	Primary	Preclinical	Unknown Approved Use Unknown
Cancer 592 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23129805	Primary	Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Effects of the calmodulin antagonists fendiline and calmidazolium on aggregation, secretion of ATP, and internal calcium in washed human platelets.	1991 Jan	2030746
Inhibitors of calmodulin impair the constitutive but not the inducible nitric oxide synthase activity in the rat aorta.	1992 May	1374468
Effects of the antianginal drug fendiline on Ca2+ movement in hepatoma cells.	2001 Jul	11530834
Fendiline, an anti-anginal drug, increases intracellular Ca2+ in PC3 human prostate cancer cells.	2001 Jul	11488522
Determination of fendiline and gallopamil by capillary isotachophoresis.	2001 Jun 15	11417865
Fendiline-Induced Ca2+ movement in A10 smooth muscle cells.	2001 Mar 31	11403516
The anti-anginal drug fendiline increases intracellular Ca(2+) levels in MG63 human osteosarcoma cells.	2001 Mar 8	11246176
Dual effect of the antianginal drug fendiline on bladder female transitional carcinoma cells: mobilization of intracellular CA2+ and induction of cell death.	2001 May	11359998
Fendiline mobilizes intracellular Ca2+ in Chang liver cells.	2001 Sep	11553031
The anti-anginal drug fendiline elevates cytosolic Ca(2+) in rabbit corneal epithelial cells.	2002 Jul 19	12088766
Arylalkylamines are a novel class of positive allosteric modulators at GABA(B) receptors in rat neocortex.	2002 Sep 6	12223231
Calcimimetic and calcilytic drugs: just for parathyroid cells?	2004 Mar	15200152
Calcium sensing receptors as integrators of multiple metabolic signals.	2004 Mar	15200144
GABA(B) receptor modulators potentiate baclofen-induced depression of dopamine neuron activity in the rat ventral tegmental area.	2005 Apr	15711597
Clinical potential of GABAB receptor modulators.	2005 Autumn	16389296
Allosteric modulation of GABA(B) receptor function in human frontal cortex.	2005 Jan	15627515
3-Chloro,4-methoxyfendiline is a potent GABA(B) receptor potentiator in rat neocortical slices.	2005 Jan 10	15659292
Spectrofluorimetric determination of fendiline in tablets.	2005 Oct	16259131
Quantitative structure-pharmacokinetic relationships for drug clearance by using statistical learning methods.	2006 Mar	16290201
2'-hydroxy-fendiline analogues as potent relaxers of isolated arteries.	2007 Apr 30	17331497
Allosteric modulators of GABA(B) receptors: mechanism of action and therapeutic perspective.	2007 Sep	19305802
Allosteric modulation of the calcium-sensing receptor.	2007 Sep	19305800
[Role of apoptosis in the kidney after reperfusion].	2008 Feb 17	18258561
Interaction of antagonists with calmodulin: insights from molecular dynamics simulations.	2008 Jun 12	18459732
Fendiline-evoked [Ca2+]i rises and non-Ca2+-triggered cell death in human oral cancer cells.	2009 Jan	19411560
LuxR-dependent quorum sensing: computer aided discovery of new inhibitors structurally unrelated to N-acylhomoserine lactones.	2010 Aug 1	20615699
Contractile actions of L-type Ca2+ agonists in human vas deferens and effects of structurally different Ca2+ antagonists.	2010 Feb 10	19878664

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:06:51 UTC 2023` Edited by `admin` on `Fri Dec 15 16:06:51 UTC 2023`
Record UNII	S253D559A8
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FENDILINE

Official Name

English

Fendiline [WHO-DD]

Common Name

English

FENDILINE [MI]

Common Name

English

fendiline [INN]

Common Name

English

N-(3,3-DIPHENYLPROPYL)-.ALPHA.-METHYLBENZYLAMINE

Systematic Name

English

Classification Tree Code System Code

WHO-VATC

QC08EA01