CAS 54143-56-5|flecainide acetate

Introduction：Basic information about CAS 54143-56-5|flecainide acetate, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. flecainide acetate BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
5. Safety Information
6. Articles46
7. Synonyms

Common Name	flecainide acetate
CAS Number	54143-56-5	Molecular Weight	474.395
Density	1.286g/cm3	Boiling Point	434.9ºC at 760mmHg
Molecular Formula	C₁₉H₂₄F₆N₂O₅	Melting Point	145-147℃
MSDS	ChineseUSA	Flash Point	216.8ºC
Symbol	GHS07, GHS08	Signal Word	Danger

Names

Name	flecainide acetate
Synonym	More Synonyms

flecainide acetate BiologicalActivity

Description	Flecainide(Tambocor) is a class 1C antiarrhythmic drug especially used for the management of supraventricular arrhythmia; works by blocking the Nav1.5 sodium channel in the heart, causing prolongation of the cardiac action potential.IC50 Value:Target: Nav1.5 channelFlecainide is a class 1C antiarrhythmic drug especially used for the management of supraventricular arrhythmia. Flecainide works by blocking the Nav1.5 sodium channel in the heart, causing prolongation of the cardiac action potential.in vitro: Under the current-clamp condition, flecainide (1-100 microM) prolonged the action potential duration at both the early and the late phases of repolarization in a concentration-dependent manner without affecting the resting membrane potential [1]. At a holding potential (HP) of -120 mV, flecainide use-dependently blocked WT and G1306E I(Na) equally but was more potent on R1448C channels. For WT, the extent of block depended on a holding voltage more negative than the activation threshold, being greater at -90 mV as compared to -120 and -180 mV [2].in vivo: Flecainide (80-130 mg/m(2) orally) resulted in termination of the tachycardia in all 8 patients. Acute pharmacological termination of arrhythmia occurred with oral flecainide loading in 1 and temporarily with intravenous esmolol loading in 1 patient. Adjuvant therapy in form of propranolol was used in 5 and digoxin in 2 [3].Clinical trial: To Evaluate the Impact of Oral Flecainide on Quality of Life in Patients With Paroxysmal Atrial Fibrillation . Phase4
Related Catalog	Signaling Pathways >>Membrane Transporter/Ion Channel >>Sodium ChannelResearch Areas >>Cardiovascular Disease
References	[1]. Yamashita T, Nakajima T, Hamada E, Flecainide inhibits the transient outward current in atrial myocytes isolated from the rabbit heart. J Pharmacol Exp Ther. 1995 Jul;274(1):315-21. [2]. Desaphy JF, De Luca A, Didonna MP, Different flecainide sensitivity of hNav1.4 channels and myotonic mutants explained by state-dependent block. J Physiol. 2004 Jan 15;554(Pt 2):321-34. [3]. Kohli V. Oral flecainide is effective in management of refractory tachycardia in infants. Indian Heart J. 2013 Mar-Apr;65(2):168-71.

Description

Flecainide(Tambocor) is a class 1C antiarrhythmic drug especially used for the management of supraventricular arrhythmia; works by blocking the Nav1.5 sodium channel in the heart, causing prolongation of the cardiac action potential.IC50 Value:Target: Nav1.5 channelFlecainide is a class 1C antiarrhythmic drug especially used for the management of supraventricular arrhythmia. Flecainide works by blocking the Nav1.5 sodium channel in the heart, causing prolongation of the cardiac action potential.in vitro: Under the current-clamp condition, flecainide (1-100 microM) prolonged the action potential duration at both the early and the late phases of repolarization in a concentration-dependent manner without affecting the resting membrane potential [1]. At a holding potential (HP) of -120 mV, flecainide use-dependently blocked WT and G1306E I(Na) equally but was more potent on R1448C channels. For WT, the extent of block depended on a holding voltage more negative than the activation threshold, being greater at -90 mV as compared to -120 and -180 mV [2].in vivo: Flecainide (80-130 mg/m(2) orally) resulted in termination of the tachycardia in all 8 patients. Acute pharmacological termination of arrhythmia occurred with oral flecainide loading in 1 and temporarily with intravenous esmolol loading in 1 patient. Adjuvant therapy in form of propranolol was used in 5 and digoxin in 2 [3].Clinical trial: To Evaluate the Impact of Oral Flecainide on Quality of Life in Patients With Paroxysmal Atrial Fibrillation . Phase4

Related Catalog

Signaling Pathways >>Membrane Transporter/Ion Channel >>Sodium ChannelResearch Areas >>Cardiovascular Disease

References

[1]. Yamashita T, Nakajima T, Hamada E, Flecainide inhibits the transient outward current in atrial myocytes isolated from the rabbit heart. J Pharmacol Exp Ther. 1995 Jul;274(1):315-21.

[2]. Desaphy JF, De Luca A, Didonna MP, Different flecainide sensitivity of hNav1.4 channels and myotonic mutants explained by state-dependent block. J Physiol. 2004 Jan 15;554(Pt 2):321-34.

[3]. Kohli V. Oral flecainide is effective in management of refractory tachycardia in infants. Indian Heart J. 2013 Mar-Apr;65(2):168-71.

Chemical & Physical Properties

Density	1.286g/cm3
Boiling Point	434.9ºC at 760mmHg
Melting Point	145-147℃
Molecular Formula	C₁₉H₂₄F₆N₂O₅
Molecular Weight	474.395
Flash Point	216.8ºC
Exact Mass	474.158936
PSA	96.89000
LogP	4.25130
InChIKey	RKXNZRPQSOPPRN-UHFFFAOYSA-N
SMILES	CC(=O)O.O=C(NCC1CCCCN1)c1cc(OCC(F)(F)F)ccc1OCC(F)(F)F
Storage condition	2-8°C
Water Solubility	Soluble in water and in anhydrous ethanol. It is freely soluble in dilute acetic acid and practically insoluble in dilute hydrochloric acid.

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: CV5792550

CHEMICAL NAME :: Benzamide, N-(2-piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy )-, monoacetate

CAS REGISTRY NUMBER :: 54143-56-5

LAST UPDATED :: 199606

DATA ITEMS CITED :: 24

MOLECULAR FORMULA :: C17-H20-F6-N2-O3.C2-H4-O2

MOLECULAR WEIGHT :: 474.45

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 40 mg/kg/2W-I

TOXIC EFFECTS :: Cardiac - arrhythmias (including changes in conduction) Cardiac - pulse rate increase, without fall in BP

REFERENCE :: AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 111,107,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 40 mg/kg

TOXIC EFFECTS :: Cardiac - EKG changes not diagnostic of specified effects Cardiac - pulse rate increase, without fall in BP Vascular - BP lowering not characterized in autonomic section

REFERENCE :: BJCPAT British Journal of Clinical Practice. (Medical News Group, 1 Bedford St., London WC2E 9HD, UK) V.10(10)- 1956- Volume(issue)/page/year: 49,218,1995

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 28 mg/kg/1W-I

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - optic nerve neuropathy

REFERENCE :: BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 291,450,1985

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 160 mg/kg

TOXIC EFFECTS :: Cardiac - arrhythmias (including changes in conduction) Cardiac - change in rate

REFERENCE :: MJAUAJ Medical Journal of Australia. (Australasian Medical Pub. Co. Ltd., 71-79 Arundel St., Glebe, N.S.W., Australia) V.1- 1914- Volume(issue)/page/year: 155,349,1991

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 56 mg/kg/1W-I

TOXIC EFFECTS :: Cardiac - other changes

REFERENCE :: AJCDAG American Journal of Cardiology. (Technical Pub. Co., 875 Third Ave., New York, NY 10022) V.1- 1958- Volume(issue)/page/year: 55,1643,1985

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 76 mg/kg

TOXIC EFFECTS :: Cardiac - pulse rate increase, without fall in BP

REFERENCE :: AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 106,807,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 1714 ug/kg/4M-C

TOXIC EFFECTS :: Cardiac - arrhythmias (including changes in conduction)

REFERENCE :: AHJOA2 American Heart Journal. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1925- Volume(issue)/page/year: 107,222,1984

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Multiple routes

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 26 mg/kg/89H-I

TOXIC EFFECTS :: Behavioral - hallucinations, distorted perceptions

REFERENCE :: PGMJAO Postgraduate Medical Journal. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1925- Volume(issue)/page/year: 62,61,1986

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Multiple routes

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 25 mg/kg/1W-I

TOXIC EFFECTS :: Cardiac - arrhythmias (including changes in conduction)

REFERENCE :: AJCDAG American Journal of Cardiology. (Technical Pub. Co., 875 Third Ave., New York, NY 10022) V.1- 1958- Volume(issue)/page/year: 53,329,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1346 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 22,967,1991

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 215 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 22,967,1991

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 16200 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 22,967,1991

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 170 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 22,967,1991

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 188 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 22,967,1991

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 23800 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 22,967,1991 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 22 gm/kg/2Y-C

TOXIC EFFECTS :: Cardiac - changes in heart weight Kidney, Ureter, Bladder - incontinence Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 73,232,1984 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 4740 mg/kg

SEX/DURATION :: male 64 day(s) pre-mating female 1-15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - menstrual cycle changes or disorders Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,1785,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 660 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,1797,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 660 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - other effects Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,1797,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1560 mg/kg

SEX/DURATION :: female 17-22 day(s) after conception lactating female 20 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition Reproductive - Maternal Effects - postpartum Reproductive - Effects on Newborn - live birth index (measured after birth)

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,1823,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 780 mg/kg

SEX/DURATION :: female 17-22 day(s) after conception lactating female 20 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - physical

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,1823,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 520 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,1815,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 130 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,1815,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 390 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,1815,1989

Safety Information

Symbol	GHS07, GHS08
Signal Word	Danger
Hazard Statements	H302-H315-H319-H335-H360
Precautionary Statements	P201-P280-P301 + P312 + P330-P305 + P351 + P338-P308 + P313
Hazard Codes	Xn
Risk Phrases	R22
Safety Phrases	22-26-36/37/39-45
RIDADR	UN 3249
WGK Germany	-
RTECS	CV5792550
Packaging Group	III
Hazard Class	6.1(b)

Articles46

Multiple modes of ryanodine receptor 2 inhibition by flecainide.

Mol. Pharmacol. 86(6) , 696-706, (2014)

Catecholaminergic polymorphic ventricular tachycardia (CPVT) causes sudden cardiac death due to mutations in cardiac ryanodine receptors (RyR2), calsequestrin, or calmodulin. Flecainide, a class I ant...

Serum flecainide S/R ratio reflects the CYP2D6 genotype and changes in CYP2D6 activity.

Drug Metab. Pharmacokinet. 30 , 257-62, (2015)

The aims of this study were to clarify whether the ratio of S- to R-flecainide (S/R ratio) in the serum flecainide concentration was associated with the stereoselectivity of flecainide metabolism, and...

A misguided 'pill in the pocket' approach with flecainide leading to cardiac arrest.

BMJ Case Rep. 2012 , doi:10.1136/bcr-2012-006868, (2012)

Synonyms

FLECAINIDE MONOACETATE

acetic acid,N-(piperidin-2-ylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide

R 818

Flecainide acetate salt

acide acétique - N-(pipéridin-2-ylméthyl)-2,5-bis(2,2,2-trifluoroéthoxy)benzamide (1:1)

N-(Piperidin-2-ylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide acetate (1:1)

EINECS 258-997-5

Flecainide acetate

N-(2-Piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide acetate (1:1)

N-(2-Piperidylmethyl)-2,5-bis-(2,2,2-trifluoroethoxy)benzamide acetate salt

UNII:M8U465Q1WQ

N-(piperidin-2-ylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide acetate

Benzamide, N-(2-piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)-, acetate (1:1)

N-(Piperidin-2-ylmethyl)-2,5-bis(2,2,2-trifluorethoxy)benzolcarboxamidacetat

Flecainide (acetate)

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