Dose-dependent inhibition of the HERG tail current is observed at -40 mV following a test pulse to +30 mV by disopyramide concentrations in the clinical range (IC50=7.23 μM) [1].

Absorption, Distribution and Excretion
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)

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.
The second type of injury is a cholestatic hepatitis that arises after 1 to 3 weeks of therapy and is characterized by jaundice and pruritus, with prominent elevations in serum alkaline phosphatase and mild-to-moderate increases in serum aminotransferase levels (Case 1). This injury may be prolonged, but reported cases have been self limited. Immunoallergic and autoimmune features are rare.
Likelihood score: B (rare but likely cause of clinically apparent liver injury).

---

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Disopyramide is sometimes found in the plasma of nursing infants at levels of 7.5% to 12.5% of the mother's levels. The N-monodesalkyldisopyramide (NMD) metabolite is more anticholinergic than disopyramide itself and appears in breastmilk in levels higher than disopyramide. However, of the cases reported, there are no reports of infant effects. Disopyramide may be used cautiously while breastfeeding when other alternatives are unacceptable. Observe the infant for anticholinergic symptoms. Infant serum concentrations can be monitored if there is any concern about drug-induced adverse effects. Theoretically, disopyramide might decrease the milk supply.
◉ Effects in Breastfed Infants
There are reports of two infants who were breast-fed without complications during maternal disopyramide use of 500 to 600 mg daily effect. Infant symptoms of crying and restlessness after meals thought by one mother to be caused by disopyramide in breastmilk were judged to be unrelated by the examining physicians.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

---

Protein Binding
50%-65%

[1]. Non-competitive Effects of Disopyramide at the Neuromuscular Junction: Evidence for Endplate Ion Channel Block. Br J Anaesth. 1987 Jun;59(6):776-83.

[2]. Clinical Pharmacokinetics of Disopyramide. Clin Pharmacokinet. May-Jun 1986;11(3):214-22.

[3]. Inhibition of HERG Potassium Channel Current by the Class 1a Antiarrhythmic Agent Disopyramide. Biochem Biophys Res Commun. 2001 Feb 9;280(5):1243-50.

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 Antiarrhythmic.
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 is a class IA anti-arrhythmic agent with cardiac depressant property. Disopyramide blocks the fast sodium channel in normal cardiac cell membranes within atrial and ventricular tissues. This slows the rate and amplitude of phase 0 depolarization and thus prolongs the duration of the action potential, thereby reducing cell excitability and conduction velocity. Further, disopyramide directly decreases the rate of diastolic (phase 4) depolarization in cells with normal or augmented automaticity. Disopyramide also blocks potassium channel and results in prolonged QT interval, thus increases the effective refractory period. This agent also possesses anticholinergic property.
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.
See also: Disopyramide Phosphate (has salt form).

---

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.

---

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.

---

Pharmacodynamics
Disopyramide is an anti-arrhythmic drug indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia that are life-threatening. At therapeutic plasma levels, disopyramide 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.

C21H29N3O

339.4745

339.231

3737-09-5

Disopyramide phosphate;22059-60-5

3114

White to off-white solid powder

1.059g/cm3

505.2ºC at 760mmHg

94.5-950C

259.4ºC

4.062

1

3

8

25

409

0

UVTNFZQICZKOEM-UHFFFAOYSA-N

InChI=1S/C21H29N3O/c1-16(2)24(17(3)4)15-13-21(20(22)25,18-10-6-5-7-11-18)19-12-8-9-14-23-19/h5-12,14,16-17H,13,15H2,1-4H3,(H2,22,25)

4-[di(propan-2-yl)amino]-2-phenyl-2-pyridin-2-ylbutanamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 250 mg/mL (~736.44 mM)

Solubility in Formulation 1: ≥ 6.25 mg/mL (18.41 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 6.25 mg/mL (18.41 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 6.25 mg/mL (18.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)