APRINDINE HCL

Originator

Amidonal,Madaus,W. Germany,1976

Uses

Aprindine is a long-acting antiarrhythmic agent, effective when administered orally or intravenously in the treatment of ventricular arrhythmias of varying etiologies.

Definition

ChEBI: Aprindine hydrochloride is a member of indanes.

Manufacturing Process

104.6 g (0.5 mol) N-phenyl-2-aminoindane and 2.5 liters benzene are introduced into a reaction vessel of 5 liters, under an atmosphere of nitrogen. 37 g (0.95 mol) sodium amide are added and the mixture is stirred during 3 hours at room temperature.
119.7 g (0.8 mol) of γ-chloropropyl diethylamine are then quickly added. After agitation during 1 hour at room temperature, the reaction mixture is refluxed and stirred under nitrogen during 21 hours. The mixture is then allowed to cool and poured onto ice. The obtained aqueous phase is extracted by means of 500 cm3 of benzene. The benzene extract is washed two times with 200 cm3 of water and the benzene is then evaporated.
The residue is treated with 500 cm3 of hydrochloric acid (2 N). The obtained solution is evaporated to dryness and the oily residue is recrystallized from ethanol. 176.9 g (yield 89.4%) of dihydrochloride of N-phenyl-Ndiethylaminopropyl- 2-aminoindane are obtained, MP 208° to 210°C.
The dihydrochloride is converted into monohydrochloride by dissolving 26.36 g (0.066 mol) of dihydrochloride into 158 cm3 of water, adding drop by drop a suitable amount (0.066 mol) of caustic soda (1 N), evaporating the aqueous solution to dryness, drying by means of benzene, filtering the formed sodium chloride (3.8 g) and crystallizing the cooled obtained benzene solution. 22.6 g (95%) of monohydrochloride are obtained, MP 120° to 121°C.

brand name

Fibocil (Lilly).

Therapeutic Function

Antiarrhythmic

Biological Activity

Aprindine hydrochloride is a class Ib antiarrhythmic and hERG channel blocker. Aprindine shows structure similarities to lidocaine and procainamide and is effective in treatment of patients with ventricular premature depolarizations, ventricular tachycardia, and supraventricular arrhythmias. Aprindine inhibits the activation of bovine brain cyclic 3μ:5μ-nucleotide phosphodiesterase (EC 3.1.4.17) by calmodulin and inhibits calmodulin-stimulated Ca-ATPase (ATP phosphohydrolase EC 3.6.1.3) activity.