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Disopyramide

Disopyramide structure

CAS No:
3737-09-5
Formula:
C21H29N3O
Chemical Name:
Disopyramide
Synonyms:
2-Pyridineacetamide,α-[2-[bis(1-methylethyl)amino]ethyl]-α-phenyl-;2-Pyridineacetamide,α-[2-(diisopropylamino)ethyl]-α-phenyl-;α-[2-[Bis(1-methylethyl)amino]ethyl]-α-phenyl-2-pyridineacetamide;SC 7031;α-[2-(Diisopropylamino)ethyl]-α-phenyl-2-pyridineacetamide;4-Diisopropylamino-2-phenyl-2-(2-pyridyl)butyramide;Disopyramide;H 3292;Dicorantil;Searle 703;(±)-Disopyramide;dl-Disopyramide;(RS)-disopyramide;Ritmilen;Lispine;Isorythm;Ritmodan;74427-45-5
Categories:
Active Pharmaceutical Ingredients > Circulatory System Drugs

Description

Disopyramide (Dicorantil) is a class IA antiarrhythmic drug with efficacy in ventricular and atrial arrhythmias. Disopyramide blocks the fast inward sodium current of cardiac muscle and prolongs the duration of cardiac action potentials. Disopyramide inhibits HERG encoded potassium channels. Disopyramide also exhibits complex protein binding, and has a potent negative inotropic action[1][2][3].

Solid

Disopyramide is a monocarboxylic acid amide that is butanamide substituted by a diisopropylamino group at position 4, a phenyl group at position 2 and a pyridin-2-yl group at position 2. It is used as a anti-arrhythmia drug. It has a role as an anti-arrhythmia drug. It is a monocarboxylic acid amide, a member of pyridines and a tertiary amino compound.|A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties.|Disopyramide is an oral antiarrhythmic agent that has been in wide use for several decades. Long term disopyramide therapy is associated with a low rate of serum enzyme elevations and is a rare cause of clinically apparent acute liver injury.

Disopyramide Basic Attributes

Molecular Weight：

339.47

Exact Mass：

339.47

EC Number：

223-110-2

DSSTox ID：

DTXSID1045536

ATC Code：

C01BA03|C - Cardiovascular system

Characteristics

PSA：

59.2

XLogP3：

3.2

Appearance：

Solid

Density：

1.059g/cm3

Melting Point：

94.5-95 °C

Boiling Point：

505.2ºC at 760mmHg

Flash Point：

259.4ºC

Water Solubility：

6.17mg/L(22.5 ºC)

Storage Conditions：

2-8°C

Toxicity：

LD50 i.p. in mice: 517 mmol/kg (Ruenitz, Mokler)

Safety Information

Transport codes：

NONH for all modes of transport

wgk germany：

hazard class code：

22-36/37/38-39/23/24/25-23/24/25-11

safety instructions：

36-26-45-36/37-16-7

RTECS Number：

UR8432000

Marks：

Xn,Xi,T,F

Precautionary statement(s)：

P280-P301 + P312 + P330

Hazard Statements：

H302-H361

GHS Classification：

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P264, P270, P281, P301+P312, P308+P313, P330, P405, and P501|Aggregated GHS information provided by 42 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Toxicity

Toxicity Summary：

LD50=580 mg/kg in rats

Hepatotoxicity：

In clinical trials, disopyramide was associated with a low rate of serum aminotransferase and alkaline phosphatase elevations. Despite wide scale use, disopyramide has only rarely been linked to cases of clinically apparent liver injury. Two types of hepatic injury have been described. The first is an acute hepatocellular injury that arises within 1 to 3 days of starting disopyramide and resembles acute hepatic ischemia with marked early rises in serum aminotransferase levels (and LDH), with minimal increase in alkaline phosphatase and subsequent rise in serum bilirubin. The prothrombin time may be abnormal initially. The injury resolves rapidly and may relate to sudden worsening of congestive heart failure due to the myocardial depressant effects of disopyramide.

Protein Binding：

50%-65%

Drug Information

Drug Indication：

For the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, ventricular pre-excitation and cardiac dysrhythmias. It is a Class Ia antiarrhythmic drug.

LiverTox Summary：

Disopyramide is an oral antiarrhythmic agent that has been in wide use for several decades. Long term disopyramide therapy is associated with a low rate of serum enzyme elevations and is a rare cause of clinically apparent acute liver injury.

Drug Classes：

Antiarrhythmic Agents

Pharmacology：

Disopyramide is an antiarrhythmic drug indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia that are life-threatening. In man, Disopyramide at therapeutic plasma levels shortens the sinus node recovery time, lengthens the effective refractory period of the atrium, and has a minimal effect on the effective refractory period of the AV node. Little effect has been shown on AV-nodal and His-Purkinje conduction times or QRS duration. However, prolongation of conduction in accessory pathways occurs.

MeSH：

A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS. (See all compounds classified as Voltage-Gated Sodium Channel Blockers.)|Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade. (See all compounds classified as Anti-Arrhythmia Agents.)

Absorption：

Nearly complete|In healthy men, about 50% of a given dose of disopyramide is excreted in the urine as the unchanged drug, about 20% as the mono-N-dealkylated metabolite and 10% as the other metabolites.

Metabolism/Metabolites：

Hepatic|Disopyramide has known human metabolites that include N-Desisopropyldisopyramide.

Biological Half-Life：

6.7 hours (range 4-10 hours)

Mechanism of Action：

Disopyramide is a Type 1A antiarrhythmic drug (ie, similar to procainamide and quinidine). It inhibits the fast sodium channels. In animal studies Disopyramide decreases the rate of diastolic depolarization (phase 4) in cells with augmented automaticity, decreases the upstroke velocity (phase 0) and increases the action potential duration of normal cardiac cells, decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium, and has no effect on alpha- or beta-adrenergic receptors.

MeSH Entry Terms：

Diisopyramide

Disopyramide Use and Manufacturing

Uses

Antiarrhythmic;Na+ channel blocker

Use Classification：

Pharmaceuticals

Computed Properties

Molecular Weight:339.5
XLogP3:3.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:8
Exact Mass:339.231062557
Monoisotopic Mass:339.231062557
Topological Polar Surface Area:59.2
Heavy Atom Count:25
Complexity:409
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes