Synthesis and Mechanism of action of Procainamide

 

Synthesis of Procainamide:

Procainamide is a derivative of procaine, with an amide group (-CONH2) replacing the ester group (-COOR). Its synthesis can be achieved through the following steps:

1. Starting Material: The synthesis typically starts with 4-aminobenzoic acid (PABA).

2. Amidation:

   • PABA is reacted with ammonia or an amine source to replace the carboxylic acid group (-COOH) with an amide group (-CONH2).
   • This is done by converting the carboxyl group into an acyl chloride intermediate (using thionyl chloride, SOCl₂) followed by treatment with ammonia (NH₃) to form the amide, giving p-aminobenzamide.

3. Esterification of Ethylamine:

   • The next step involves attaching a chain of ethylamine at the para-position of the aromatic ring. This is achieved through the nucleophilic substitution of an alkyl halide (ethyl bromide or ethyl chloride) with the amino group at the 4-position of the benzene ring.

4. Final Compound: The result is procainamide with the structure of 4-(aminophenyl)-2-propionamide.

Mechanism of Action of Procainamide:

Procainamide is classified as a Class 1A antiarrhythmic agent. Its primary mechanism of action involves blocking sodium (Na⁺) channels in the heart. Here's a detailed explanation of its mechanism:

1. Sodium Channel Blockade:

   • Procainamide inhibits the fast inward sodium current (I_Na) by blocking voltage-gated sodium channels in their open and inactive states.
   • This action slows the rate of depolarization during phase 0 of the cardiac action potential, resulting in a reduced rate of rise of the action potential and a decrease in conduction velocity.

2. Prolongation of Action Potential:

   • It also prolongs the repolarization phase (phase 3) by increasing the refractory period. This is due to its effects on potassium channels, causing a delay in repolarization.

3. Effect on the ECG:

   • Procainamide's action results in prolongation of the QRS complex and the QT interval on the electrocardiogram (ECG), reflecting its effect on conduction velocity and repolarization time.

4. Antiarrhythmic Effects:

   • By slowing conduction and prolonging repolarization, procainamide can correct abnormal heart rhythms such as ventricular tachycardia, atrial fibrillation, and paroxysmal supraventricular tachycardia.
   • It works by reducing the excitability of cardiac tissue, preventing the re-entry of electrical impulses that cause arrhythmias.

Overall, procainamide's mechanism of action stabilizes cardiac membranes and reduces the likelihood of abnormal electrical impulses triggering arrhythmias.