TEDISAMIL SESQUIFUMARATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	2C19H32N2.3C4H4O4
Molecular Weight	925.158
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	3
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.C(C1CC1)N2CC3CN(CC4CC4)CC(C2)C35CCCC5.C(C6CC6)N7CC8CN(CC9CC9)CC(C7)C8%10CCCC%10

InChI

InChIKey=AZPYPAVFNGFTGB-VQYXCCSOSA-N

InChI=1S/2C19H32N2.3C4H4O4/c2*1-2-8-19(7-1)17-11-20(9-15-3-4-15)12-18(19)14-21(13-17)10-16-5-6-16;3*5-3(6)1-2-4(7)8/h2*15-18H,1-14H2;3*1-2H,(H,5,6)(H,7,8)/b;;3*2-1+

HIDE SMILES / InChI

Description
Sources: https://www.fdanews.com/articles/102230-advisory-committee-recommends-no-approval-for-pulzium?v=preview | https://clinicaltrials.gov/ct2/show/NCT00126061 | http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con031129.pdf | https://www.ncbi.nlm.nih.gov/pubmed/14996649 | https://www.ncbi.nlm.nih.gov/pubmed/11527020

Tedisamil is an antiarrhythmic with additional anti-ischaemic properties, which acts via potassium channel blockade. This drug can be categorised as a class III antiarrhythmic agent due to its effects of action potential and QT interval prolongation in these patients. Although tedisamil has been shown to be an effective anti-ischaemic agent, with Phase III trials for angina pectoris now completed, the company are now pursuing the use of tedisamil for the treatment of atrial fibrillation, for which tedisamil is still in Phase II/III clinical trials. The FDA’s Cardiovascular and Renal Drugs Advisory Committee voted not to recommend approval for Solvay Pharmaceuticals’ investigational anti-arrhythmic drug Pulzium (Tedisamil) and asked the company to give the FDA more information.

Originator

Approval Year

PubMed

Title	Date	PubMed
Genomic organization, chromosomal localization, tissue distribution, and biophysical characterization of a novel mammalian Shaker-related voltage-gated potassium channel, Kv1.7.	1998 Mar 6	9488722
Tedisamil and dofetilide-induced torsades de pointes, rate and potassium dependence.	2001 Apr	11264243
Tedisamil (Solvay).	2001 Jan	11527020
Effects of tedisamil on cardiovascular tissues isolated from normo- and hypertensive rats.	2001 Jul	11584333
Transgenic mice overexpressing human KvLQT1 dominant-negative isoform. Part II: Pharmacological profile.	2001 May	11334836
Newer antiarrhythmic drugs.	2001 May-Jun	11516042
Conversion of atrial fibrillation by the experimental antiarrhythmic drug tedisamil in two canine models.	2001 Oct	11699522
Tedisamil blocks BK-type Ca(2+)-dependent K(+) channels and modulates action potentials in rat hippocampal neurons.	2002 Feb 15	11825675
Tedisamil in coronary disease: additional benefits in the therapy of atrial fibrillation?	2003 Jun	12746750
Trial finds new anti-arrhythmic, tedisamil, is superior to placebo for converting recent onset atrial fibrillation or atrial flutter.	2004 Dec	16379966
Effect of the antifibrillatory compound tedisamil (KC-8857) on transmembrane currents in mammalian ventricular myocytes.	2004 Dec	15579009
Electrical storms in Brugada syndrome: review of pharmacologic and ablative therapeutic options.	2005 Jan 1	16943940
New antiarrhythmic treatment of atrial fibrillation.	2007 Jul	17605649
Relationship among amiodarone, new class III antiarrhythmics, miscellaneous agents and acquired long QT syndrome.	2008	18651412
Update on atrial fibrillation: part II.	2008 Mar	18383050
New horizons in antiarrhythmic therapy: will novel agents overcome current deficits?	2008 Sep 22	18790110
Recent advances in pharmacotherapy of atrial fibrillation.	2009 Aug	20523864
Novel antiarrhythmic drugs in atrial fibrillation: focus on tedisamil.	2009 Aug	19604120
The transmembrane beta-subunits KCNE1, KCNE2, and DPP6 modify pharmacological effects of the antiarrhythmic agent tedisamil on the transient outward current Ito.	2009 Jun	19153714
Clinically important interaction between tedisamil and verapamil.	2009 May	19299533
Atrial fibrillation: from ion channels to bedside treatment options.	2009 Nov-Dec	19520377

Sample Use Guides

In Vivo Use Guide

The recommended dose is 0.32 mg/kg

Route of Administration: Intravenous

Name

Type

Language

TEDISAMIL SESQUIFUMARATE

Official Name

English

KC-8857 SESQUIFUMARATE

Code

English

TEDISAMIL SESQUIFUMARATE [USAN]

Common Name

English

Tedisamil sesquifumarate [WHO-DD]

Common Name

English

PULZIUM

Brand Name

English

SPIRO(CYCLOPENTANE-1,9'-(3,7)DIAZABICYCLO(3.3.1)NONANE), 3',7'-BIS(CYCLOPROPYLMETHYL)-, (2E)-2-BUTENEDIOATE (2:3)

Common Name

English

TEDISAMIL SESQUIFUMARATE [MI]

Common Name

English

BIS(3',7'-BIS(CYCLOPROPYLMETHYL)SPIRO(CYCLOPENTANE-1,9'-(3,7)DIAZABICYCLO(3.3.1)NONANE))DIHYDROGEN TRIS((2E-BUT-2-ENEDIOATE)

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C93038