flecainide acetate

Modify Date: 2024-01-05 17:38:19

flecainide acetate Structure
flecainide acetate structure
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 Chinese USA Flash Point 216.8ºC
Symbol GHS07 GHS08
GHS07, GHS08
Signal Word Danger

 Use of flecainide acetate


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

 Names

Name flecainide acetate
Synonym More Synonyms

 flecainide acetate Biological Activity

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
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
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
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)

 Synthetic Route

~87%

flecainide acetate Structure

flecainide acetate

CAS#:54143-56-5

Literature: "Joint Stock Company Grindeks" Patent: EP1918280 A1, 2008 ; Location in patent: Page/Page column 4; 8 ;

~87%

flecainide acetate Structure

flecainide acetate

CAS#:54143-56-5

Literature: Geneva Pharmaceuticals, Inc. Patent: US6458957 B1, 2002 ;

~87%

flecainide acetate Structure

flecainide acetate

CAS#:54143-56-5

Literature: Wang, Zhi-Xian; Li, Yuanqiang; Guntoori, Bhaskar Reddy Patent: US2005/59825 A1, 2005 ; Location in patent: Page/Page column 4 ;

 Articles46

More Articles
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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