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
Almost completely. In healthy men, after taking a dose of disopyramide, approximately 50% is excreted unchanged in the urine, approximately 20% is excreted as a monodealkylated metabolite, and 10% is excreted as other metabolites. Metabolism/Metabolites Hepatic Metabolism. Known human metabolites of disopyramide include N-deisopropyldisopyramide. Biological Half-Life 6.7 hours (range 4–10 hours)

Hepatotoxicity
In clinical trials, disopyramide was associated with a low incidence of elevated serum transaminases and alkaline phosphatases. Despite its widespread use, clinically significant cases of liver injury are rare. Two types of liver injury have been described. The first is acute hepatocellular injury, which typically occurs within 1 to 3 days after starting disopyramide treatment. It resembles acute hepatic ischemia, characterized by an early, significant increase in serum transaminase (and lactate dehydrogenase) levels, a smaller increase in alkaline phosphatase, followed by an increase in serum bilirubin. Prothrombin time may initially be abnormal. This injury resolves rapidly, possibly due to a sudden exacerbation of congestive heart failure caused by the myocardial depressant effect of disopyramide. The second type of injury is cholestatic hepatitis, which usually occurs 1 to 3 weeks after treatment. It is characterized by jaundice and pruritus, a significant increase in serum alkaline phosphatase, and a mild to moderate increase in serum transaminase levels (Case 1). This injury may be prolonged, but all reported cases are self-limiting. Immune hypersensitivity and autoimmune features are rare.
Probability Score: B (Rare but likely a cause of clinically significant liver injury).

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Effects during Pregnancy and Lactation
◉ Overview of Use During Lactation
Disopyramide is sometimes detected in the plasma of nursing infants at concentrations ranging from 7.5% to 12.5% of the maternal concentration. The anticholinergic effects of the N-monodesyldiisopropyramide (NMD) metabolite are stronger than those of diisopropyramide itself, and its concentration in breast milk is higher than that of diisopropyramide. However, there are no reported cases of infants being affected in reported cases. Diisopropyramide should be used with caution by nursing women when other alternative medications are not feasible. The infant should be closely monitored for anticholinergic symptoms. Infant serum drug concentrations should be monitored if there are any concerns about adverse drug reactions. Theoretically, diisopropyramide may reduce milk production.
◉ Effects on Breastfed Infants
It has been reported that two infants breastfed without complications while their mothers were taking 500 to 600 mg of diisopyramide daily. One mother believed that her infant's post-feeding crying and irritability were caused by disopyramide in breast milk, but the examining physician determined that this was unrelated.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

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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 with the structure butyramide, substituted at the 4-position with a diisopropylamino group, at the 2-position with a phenyl group, and at the 3-position with a pyridin-2-yl group. It is an antiarrhythmic drug. Disopyramide is a monocarboxylic acid amide, belonging to the pyridine class of compounds, and is also a tertiary amine compound. It is a Class I antiarrhythmic drug (directly interfering with myocardial cell membrane depolarization, thus acting as a membrane stabilizer), and its cardiac depressant effect is similar to that of guanidine. It also has certain anticholinergic and local anesthetic effects. Disopyramide is an oral antiarrhythmic drug that has been widely used for decades. The incidence of elevated serum enzymes with long-term disopyramide treatment is low, and it is a rare cause of clinically significant acute liver injury. Disopyramide is a Class IA antiarrhythmic drug with cardiac depressant effects. Disopyramide blocks fast sodium channels on normal myocardial cell membranes, including atrial and ventricular tissues. This slows the rate and amplitude of phase 0 depolarization, thereby prolonging the duration of the action potential and reducing cellular excitability and conduction velocity. Furthermore, disopyramide can directly reduce the rate of diastolic (phase 4) depolarization in normal or enhanced automaticity cells. Disopyramide can also block potassium channels, leading to QT interval prolongation and thus increasing the effective refractory period. This drug also has anticholinergic properties. It is a Class I antiarrhythmic drug (directly interfering with myocardial cell membrane depolarization, thus acting as a membrane stabilizer), with cardiac inhibitory effects similar to guanidine. It also has some anticholinergic and local anesthetic effects. See also: diisopropylpyramide phosphate (in salt form).

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Indications
For the treatment of diagnosed ventricular arrhythmias, such as sustained ventricular tachycardia, ventricular pre-excitation, and other arrhythmias. It is a Class Ia antiarrhythmic drug. Mechanism of Action
Diisopyramide is a type Ia antiarrhythmic drug (i.e., similar to procainamide and quinidine). It inhibits fast sodium channels. Animal studies have shown that disopyramide can reduce the diastolic depolarization rate (phase 4) of automaticity-enhancing cells, reduce the rise rate (phase 0) of normal cardiomyocytes, prolong the action potential duration, reduce the refractory period difference between infarcted myocardium and adjacent normal perfused myocardium, and has no effect on α or β adrenergic receptors.
Pharmacodynamics
Disopyramide is an antiarrhythmic drug indicated for the treatment of diagnosed ventricular arrhythmias, such as life-threatening sustained ventricular tachycardia. At therapeutic plasma concentrations, disopyramide can shorten the sinoatrial node recovery time, prolong the atrial effective refractory period, and has little effect on the atrioventricular node effective refractory period. Disopyramide also has little effect on the atrioventricular node and His-Purkinje conduction time or QRS duration. However, prolongation of accessory pathway conduction is sometimes observed.

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.

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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.

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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.

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