Procainamide hydrochloride is a white or light yellow crystalline powder with a melting point of 165–169 °C. It is soluble in water and ethanol, slightly soluble in chloroform, and very slightly soluble in ether or benzene. It is odorless and hygroscopic.
Procainamide hydrochloride (PAH) is suitable to investigate its binding behavior with human serum albumin and bovine serum albumin by fluorescence quenching study to understand the pharmacokinetic and pharmacodynamic mechanisms of PAH.
ChEBI: A hydrochloride which has procainamide as the amino component.
Procainamide hydrochloride,p-amino-N-[2-(diethylamino)ethyl]benzamidemonohydrochloride, procainamidium chloride (Pronestyl,Procan SR), has emerged as a major antiarrhythmic drug. Itwas developed in the course of research for compoundsstructurally similar to procaine, which had limited effectas an antiarrhythmic agent because of its central nervoussystem (CNS) side effects and short-lived action causedby rapid hydrolysis of its ester linkage by plasma esterases.Because of its amide structure, procainamide hydrochlorideis also more stable in water than is procaine. Aqueoussolutions of procainamide hydrochloride have a pH ofabout 5.5. A kinetic study of the acid-catalyzed hydrolysisof procainamide hydrochloride showed it to be unusuallystable to hydrolysis in the pH range 2 to 7, even at elevatedtemperatures.
Procainamide hydrochloride is a sodium channel blocker and Class IA anti-arrhythmic. It has also been shown to Inhibit DNA methyltransferase and modulate epigenetic regulation of gene expression.
Procainamide hydrochloride is metabolized through theaction of N-acetyltransferase. The product of enzymaticmetabolism of procainamide hydrochloride is N-acetylprocainamide(NAPA), which possesses only 25% of the activityof the parent compound. A study of the disposition ofprocainamide hydrochloride showed that 50% of the drugwas excreted unchanged in the urine, with 7% to 24% recoveredas NAPA. Unlike quinidine, procainamide hydrochlorideis bound only minimally to plasma proteins.Between 75% and 95% of the drug is absorbed from the gastrointestinaltract. Plasma levels appear 20 to 30 minutesafter administration and peak in about 1 hour. Procainamide hydrochloride appears to have all of theelectrophysiological effects of quinidine. It diminishesautomaticity, decreases conduction velocity, and increasesaction potential duration and, thereby, the refractory periodof myocardial tissue. Clinicians have favored the use of procainamidehydrochloride for ventricular tachycardias andquinidine for atrial arrhythmias, even though the two drugsare effective in either type of disorder.
Procainamide was initially synthesized using 4-nitrobenzoyl chloride as the starting material, and then many new synthesis methods appeared in the following decades, such as 4-nitrobenzoic acid, diethylaminoethylamine and so on as the starting material for the synthesis. However, these synthetic routes have low yields and the products are difficult to purify, which leads to industrial difficulties in production and is difficult to apply to large-scale industrial production.
Veterinary Drugs and Treatments
Procainamide potentially may be useful for the treatment of ventricular
premature complexes (VPC’s), ventricular tachycardia,
or supraventricular tachycardia associated with Wolff-Parkinson-
White (WPW) syndrome with wide QRS complexes. Higher doses
may be beneficial in the treatment of supraventricular tachycardias,
although procainamide cannot be considered a first-line agent for
this dysrhythmia.
Procainamide Hydrochloride is the hydrochloride salt form of procainamide, an amide derivative exhibiting class 1A antiarrhythmic property and analog of procaine. Procainamide hydrochloride reversibly binds to and blocks activated (open) voltage-gated sodium channels, thereby blocks the influx of sodium ions into the cell, which leads to an increase in threshold for excitation and inhibit depolarization during phase 0 of the action potential. In addition, the effective refractory period (ERP), action potential duration (APD), and ERP/APD ratios are increased, resulting in decreased impulse conduction velocity. The lasting action potential may also be due to blockage of outward K+ currents. The result is a decrease in automaticity, increase in refractory period and slowing of impulse conduction.
[1] KIRTHI BYADAGI. Investigation of binding behaviour of procainamide hydrochloride with human serum albumin using synchronous, 3D fluorescence and circular dichroism[J]. Journal of Pharmaceutical Analysis, 2017, 7 2: Pages 103-109. DOI:
10.1016/j.jpha.2016.07.004.
[2] M. METI. Investigation of the interaction of the new antiarrhythmic drug procainamide hydrochloride with bovine serum albumin and the effect of some metal ions on the binding: a fluorescence quenching study[J]. Monatshefte für Chemie - Chemical Monthly, 2013, 163 1: 1253-1259. DOI:
10.1007/s00706-013-0933-7.
