Search for New Antiarrhythmic and Hypotensive Compounds. Synthesis,Antiarrhythmic, Antihypertensive,and α-Adrenoceptor Blocking Activity of Novel 1-[(2-Hydroxy-3-amino)]-propylpyrrolidin-2-one Derivatives

A series of the derivatives of 1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl]-pyrrolidin-2-one ( MG-1 ) was synthesized and tested for electrocardiographic, antiarrhythmic, and antihypertensive activity as well as for α₁- and α₂- adrenoceptors binding affinities. Some of the compounds of this series slightly decreased the heart rate, prolonged P-Q, Q-T intervals and QRS complex. Only compound 7 (1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl]-pyrrolidine) possesses potent antiarrhythmic and a slight hypotensive properties, and affinity for α₁- and α₂- adrenoceptor. The results suggest that the antiarrhythmic and hypotensive effect of compound 7 and MG-1 is related to their adrenolytic properties, and that those properties depend on the presence of a phenylpiperazine moiety.