A new series of antiarrhythmic procainamide derivatives: toxicity and activity-simulated passive absorption relation.
Several compounds derived from benzamidines and nicotinic pyridinic amidines with a structure similar to that of procainamide, exhibit notable antiarrhythmic properties after injection into animals. The diffusion rate of these different compounds through a solid lipidic artificial membrane was studied with Dibbern's apparatus. A statistical relation was established between the diffusion rate and the principal pharmacological parameters obtained after intraperitoneal injection (toxicity and anthiarrhythmic activity). Essential structural elements seem to determine a better bioavailability than procainamide: character of the substitution (in para) of the benzenic cycle; length of the lateral chain.
Brazier
M
M
Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté de Pharmacie, Amiens.
Lefebvre
C
C
Robert
H
H
Reynaud
P
P
Nguyen-Tri-Xuong
E
E
Arnould-Guérin
M L
ML
Pieri
F
F
D000042:Absorption; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity; D001682:Biological Availability; D004058:Diffusion; D007928:Lethal Dose 50; D008567:Membranes, Artificial; D051379:Mice; D011342:Procainamide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity
D000889:Anti-Arrhythmia Agents; D008567:Membranes, Artificial; D011342:Procainamide