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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/11/13 18:59:01」(JST)

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Pilsicainide (INN) is an antiarrhythmic agent. It is marketed in Japan as サンリズム (Sunrythm). The JAN is pilsicainide hydrochloride.

Pilsicainide is a drug used clinically in Japan to treat cardiac arrhythmias. It functions by blocking the fast inward movement of sodium ions through the Nav1.5 sodium channel^[1] that contributes to the rapid depolarization characteristic of phase 0 in the cardiac action potential. Pilsicainide is a pure sodium channel blocker, meaning it does not significantly affect any other cardiac channels including potassium and calcium channels.^[2] Pilsicainide binds to a common site on the sodium channel through either intracellular or extracellular application(3). The affinity of pilsicainide for the sodium channel receptor and its rate of binding are dependent on the state of the channel. It has been proven to have a greater affinity for the receptor in its inactivated state as opposed to resting or open(4), thereby following the modulated receptor hypothesis(5). Binding of pilsicainide selectively inhibits the channel(6), preventing the movement of sodium ions into the cardiac cell. This decreases the rate of depolarization of the cell membrane as well as the action potential amplitude, but has no effect on the overall duration of the action potential(6). Suppression of the depolarization rate is use-dependent(7), and therefore inhibition increases with increased stimulation. Pilsicainide also causes delayed impulse conduction through the myocardium in a dose-dependent manner(8). The effects of pilsicainide have a slow rate of onset and offset resulting in a prolonged recovery time(9). This contributes to its potent blocking activity and its classification as a class 1c antiarrhythmic agent(10). A cardiac arrhythmia includes any abnormal heartbeat and can be manifested as tachycardia, bradycardia, or other irregular rhythms. Pilsicainide has been proven successful in treating both ventricular(11) and supraventricular arrhythmias with few adverse effects(12). It is especially effective in the treatment of atrial fibrillation.^[3] Atrial fibrillation is the most common type of arrhythmia(14). It may result from various heart abnormalities or may occur spontaneously in a seemingly healthy individual(15). Atrial fibrillation is characterized by rapid, disorganized electrical impulses in the atria resulting in depolarization of only a small group of myocardial cells. This prevents the atria from undergoing coordinated contraction, instead resulting in small fibrillations of the heart muscle. Re-entry occurs when an impulse does not die after activating the heart but instead returns to the atria and causes re-excitation(16). Simultaneous re-entry of multiple impulses with short wavelengths results in atrial fibrillation(17). Impulse wavelength is the product of the conduction velocity and the effective refractory period. Pilsicainide suppresses atrial conduction velocity but also increases the effective refractory period(18). Its effects on the refractory period are significantly more substantial, and therefore pilsicainide treatment results in an increased wavelength and termination of atrial fibrillation.^[4] A single oral dose of pilsicainide effectively restores normal sinus rhythm in patients with recent-onset atrial fibrillation and a healthy left ventricle.^[5] Long-term therapy with pilsicainide is successful in treating chronic atrial fibrillation).^[6]

3. Hattori Y, and Inomata N. Modes of the Na channel blocking action of pilsicainide, a new antiarrhythmic agent, in cardiac cells. Jpn J Pharmacol. 1992;58(4):365-73.

4. Desaphy JF, Dipalma A, Costanza T, Bruno C, Lentini G, Franchini C, George A, and Conte Camerino D. Molecular determinants of state-dependent block of voltage-gated sodium channels by pilsicainide. Br J Pharmacol. 2010;160(6):1521-33.

5. Hille B. Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol. 1977;69:497-515.

6. Hattori Y, Inomata N, Aisaka K, Ishihara T. Electrophysiological actions of N-(2,6-dimethylphenyl)-8-pyrrolizidine-acetamide hydrochloride hemihydrate (SUN 1165), a new antiarrhythmic agent. J Cardiovasc Pharmacol. 1986;8(5):998-1002.

7. Courtney KR. Interval-dependent effects of small antiarrhythmic drugs on excitability of guinea-pig myocardium. J Mol Cell Cardiol. 1980;12(11):1273-86.

8. Hidaka T, Hamasaki S, Aisaka K, Ishihara T, Morita M, Toyama J, and Yamada K. N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165), a new antiarrhythmic agent: effects on cardiac conduction. Arzneimittelforschung. 1985;35(9):1381-6.

9. Hattori Y, Hidaka T, Aisaka K, Satoh F, and Ishihara T. Effect of SUN 1165, a new potent antiarrhythmic agent, on the kinetics of rate-dependent block of Na channels and ventricular conduction of extrasystoles. J Cardiovasc Pharmacol. 1988;11(4):407-12.

10. Campbell TJ. Kinetics of onset of rate-dependent effects of class I antiarrhythmic drugs are important in determining their effects on refractoriness in guinea-pig ventricle, and provide a theoretical basis for their subclassification. Cardiovasc Res. 1983;17(6):344-52.

11. Hashimoto H, Satoh N, and Nakashima M. Effects of SUN-1165, N-(2,6-dimethylphenyl)-8-pyrrolizidine acetamide hydrochloride hemihydrate, a new class I antiarrhythmic drug, on ventricular arrhythmias, intraventricular conduction, and the refractory period in canine myocardial infarction. J Cardiovasc Pharmacol. 1992;19(3):417-24.

12. Ino T, Atarashi H, Kuruma A, Onodera T, Saitoh H, and Hayakawa H. Electrophysiologic and hemodynamic effects of a single oral dose of pilsicainide hydrochloride, a new class 1c antiarrhythmic agent. J Cardiovasc Pharmacol. 1998;31(1):157-64.

14. Feinberg WM, Blackshear JL, Laupacis A, Kronmal R, and Hart RG. Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Arch Intern Med. 1995;155(5):469-73.

15. Dang D, Arimie R, and Haywood LJ. A review of atrial fibrillation. J Natl Med Assoc. 2002;94(12):1036-48.

16. Veenhuyzen GD, Simpson CS, and Abdollah H. Atrial Fibrillation. Can Med Assoc J. 2004;171(7):755-60.

17. Rensma PL, Allessie MA, Lammers WJ, Bonke FI, and Schalij MJ. Length of excitation wave and susceptibility to reentrant atrial arrhythmias in normal conscious dogs. Circ Res. 1988;62(2):395-410.

18. Kanki H, Mitamura H, Takatsuki S, Sueyoshi K, Shinagawa K, Sato T, and Ogawa S. Postrepolarization refractoriness as a potential anti-atrial fibrillation mechanism of pilsicainide, a pure sodium channel blocker with slow recovery kinetics. Cardiovasc Drugs Ther. 1998;12(5):475-82.

References

^ Inomata N, Ishihara T, and Akaike N. SUN 1165: a new antiarrhythmic Na current blocker in ventricular myocytes of guinea-pig. Comp Biochem Physiol C. 1987;87(2):237-43.
^ Yamashita T, Murakawa Y, Sezaki K, Hayami N, Inoue M, Fukui E, and Omata M. Uniqueness of pilsicainide in class Ic antiarrhythmics. Jpn Heart J. 1998;39(3):389-97.
^ Atarashi H, Inoue H, Hiejima K, and Hayakawa H. Conversion of recent-onset atrial fibrillation by a single oral dose of pilsicainide (pilsicainide suppression trial on atrial fibrillation). Am J Cardiol. 1996;78(6):694-7.
^ Shinagawa K, Mitamura H, Takeshita A, Sato T, Kanki H, Takatsuki S, and Ogawa S. Determination of refractory periods and conduction velocity during atrial fibrillation using atrial capture in dogs: direct assessment of the wavelength and its modulation by a sodium channel blocker, pilsicainide. J Am Coll Cardiol. 2000;35(1):246-53.
^ Atarashi H, Inoue H, Hiejima K, and Hayakawa H. Conversion of recent-onset atrial fibrillation by a single oral dose of pilsicainide (pilsicainide suppression trial on atrial fibrillation). Am J Cardiol. 1996;78(6):694-7.
^ Okishige K, Nishizaki M, Azegami K, Igawa M, Yamawaki N, and Aonuma K. Pilsicainide for conversion and maintenance of sinus rhythm in chronic atrial fibrillation: a placebo-controlled, multicenter study. Am Heart J. 2000;140(3):e13.

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1. ブルガダ症候群：臨床症状、診断、評価 brugada syndrome clinical presentation diagnosis and evaluation

English Journal

Time-to-Onset Analysis of Drug-Induced Long QT Syndrome Based on a Spontaneous Reporting System for Adverse Drug Events.

Sasaoka S1, Matsui T1, Hane Y1, Abe J1,2, Ueda N1, Motooka Y1, Hatahira H1, Fukuda A1, Naganuma M1, Hasegawa S1, Kinosada Y3, Nakamura M1.
PloS one.PLoS One.2016 Oct 10;11(10):e0164309. doi: 10.1371/journal.pone.0164309. eCollection 2016.
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PMID 27723808

Right coronary cusp as a new window of ablation for pilsicainide-induced ventricular premature contractions in a patient with Brugada syndrome.

Yamasaki H1, Tada H2, Sekiguchi Y3, Aonuma K3.
Heart and vessels.Heart Vessels.2016 Aug;31(8):1397-401. doi: 10.1007/s00380-015-0760-3. Epub 2015 Oct 28.
A previous study demonstrated that ventricular premature contractions (VPCs) and ventricular fibrillation (VF) are provoked during sodium channel blocker challenge tests in Brugada syndrome (BrS) patients (Morita et al., J Am Coll Cardiol 42:1624-1631, 2003). The right ventricular outflow tract (RVO
PMID 26510553

A Novel SCN5A Mutation Associated with Drug Induced Brugada Type ECG.

Turker I1, Makiyama T2, Vatta M3, Itoh H4, Ueyama T5, Shimizu A5, Ai T1,6, Horie M4.
PloS one.PLoS One.2016 Aug 25;11(8):e0161872. doi: 10.1371/journal.pone.0161872. eCollection 2016.
BACKGROUND: Class IC antiarrhythmic agents may induce acquired forms of Brugada Syndrome. We have identified a novel mutation in SCN5A, the gene that encodes the α-subunit of the human cardiac sodium channel (hNav1.5), in a patient who exhibited Brugada- type ECG changes during pharmacotherapy of a
PMID 27560382

Japanese Journal

ダビガトラン内服中に生じた大腸粘膜下血腫の1例

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日本消化器内視鏡学会雑誌 57(6), 1373-1377, 2015
症例は66歳，女性．排便時に突然血便を認めたため夜間救急外来を受診した．1年前より発作性心房細動に対して，ダビガトラン内服が開始された．当院での初回大腸内視鏡検査で，S状結腸に茎様の構成成分を伴う粘膜下血腫を認めたため，同部位が出血源と考え入院後ダビガトランを中止し，絶食・補液管理にて経過観察とした．その後血便はなく，保存的加療のみで軽快した．心房細動に対してはダビガトラン中止のままピルシカイニド …
NAID 130005085959

Brugada Syndrome Combined with Monomorphic Ventricular Tachycardia and Atrioventricular Nodal Reentrant Tachycardia

Goto Masayuki,Sato Masahito,Kitazawa Hitoshi,Komatsu Yasushi,Fuse Koichi,Takahashi Minoru,Okabe Masaaki,Yamashina Akira,Aizawa Yoshifusa
Internal Medicine 54(10), 1223-1226, 2015
A 41-year-old man developed sustained monomorphic ventricular tachycardia (VT) with a left bundle branch block and inferior axis pattern during treadmill exercise concomitantly with unmasking of the t …
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ピルジカイニドで誘発されアブレーションし得た発熱誘発性心室頻拍の1例

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心臓 46(4), 530-535, 2014
症例は11歳, 男児. 生来健康. 心奇形なし. 4歳より37°C以上の発熱時に左脚ブロック下方軸, 心拍数170-200回/分の持続性心室頻拍を繰り返し, ベラパミル投与と解熱により停止していた. 5歳時に心臓電気生理学的検査を施行. 心室頻拍は心室プログラム刺激, イソプロテレノール負荷, 硫酸アトロピン投与では誘発されなかった. プロプラノロールを内服したが発作を繰り返したため, 10歳 …
NAID 130005060563

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★リンクテーブル★

リンク元	「ピルジカイニド」
拡張検索	「pilsicainide hydrochloride」

「ピルジカイニド」

Pilsicainide
Systematic (IUPAC) name
	N-(2,6-dimethylphenyl)-2-(tetrahydro-1H-pyrrolizin-7a(5H)-yl)acetamide
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy cat.	?
Legal status	?
Routes	Oral, IV
Identifiers
CAS number	88069-67-4
ATC code	None
PubChem	CID 4820
UNII	AV0X7V6CSE
KEGG	D08377
ChEMBL	CHEMBL163238
Chemical data
Formula	C17H24N2O
Mol. mass	272.38 g/mol
	SMILES CC1=C(C(=CC=C1)C)NC(=O)CC23CCCN2CCC3;
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英: pilsicainide
同: ピルシカイニド(添付文章としてはこちらの名称)
化: 塩酸ピルシカイニド pilsicainide hydrochloride
商: アリスリズム、サンリズム、タツピルジン、ピルジニック、リズムコート、リズムサット
関: 抗不整脈薬; 不整脈用剤

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「pilsicainide hydrochloride」

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塩酸ピルジカイニド、塩酸ピルシカイニド

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[1] Inomata N, Ishihara T, and Akaike N. SUN 1165: a new antiarrhythmic Na current blocker in ventricular myocytes of guinea-pig. Comp Biochem Physiol C. 1987;87(2):237-43.

[2] Yamashita T, Murakawa Y, Sezaki K, Hayami N, Inoue M, Fukui E, and Omata M. Uniqueness of pilsicainide in class Ic antiarrhythmics. Jpn Heart J. 1998;39(3):389-97.

[3] Atarashi H, Inoue H, Hiejima K, and Hayakawa H. Conversion of recent-onset atrial fibrillation by a single oral dose of pilsicainide (pilsicainide suppression trial on atrial fibrillation). Am J Cardiol. 1996;78(6):694-7.

[4] Shinagawa K, Mitamura H, Takeshita A, Sato T, Kanki H, Takatsuki S, and Ogawa S. Determination of refractory periods and conduction velocity during atrial fibrillation using atrial capture in dogs: direct assessment of the wavelength and its modulation by a sodium channel blocker, pilsicainide. J Am Coll Cardiol. 2000;35(1):246-53.

[5] Atarashi H, Inoue H, Hiejima K, and Hayakawa H. Conversion of recent-onset atrial fibrillation by a single oral dose of pilsicainide (pilsicainide suppression trial on atrial fibrillation). Am J Cardiol. 1996;78(6):694-7.

[6] Okishige K, Nishizaki M, Azegami K, Igawa M, Yamawaki N, and Aonuma K. Pilsicainide for conversion and maintenance of sinus rhythm in chronic atrial fibrillation: a placebo-controlled, multicenter study. Am Heart J. 2000;140(3):e13.

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pilsicainide