Pattern of interaction between dihydropyridine calcium antagonists and cationic amphiphilic drugs in isolated guinea-pig left atria.
The pharmacodynamic interaction between dihydropyridine calcium antagonists and several cationic amphiphilic agents with respect to their negative inotropic action has been studied in isolated guinea-pig left atria. (+/-)-Bepridil (CAS 64706-54-3), (+/-)-cis-diltiazem (CAS 33286-22-5), falipamil (CAS 77862-92-1), (+/-)-gallopamil (CAS 16662-47-2), lidocaine (CAS 6108-05-0), procainamide (CAS 614-39-1), or quinidine (CAS 50-54-4) were added at fixed concentrations. Afterwards, concentration-response curves for nifedipine (CAS 21829-25-4), the S-enantiomer niguldipine.HCl and its R-enantiomer dexniguldipine.HCl (CAS 113165-32-5), (+/-)-nimodipine (CAS 66085-59-4) (+/-)-nitrendipine (CAS 39562-70-4), or (+/-)-isradipine (CAS 75695-93-1) were obtained. In most cases, a left-ward shift in the concentration-response curve of the dihydropyridine was observed. The extent of this shift varied between dihydropyridines, and it depended on the catamphiphilic compound present. A high correlation was found between the different dihydropyridines, when comparing the extent of displacement of their concentration-response curves by the various catamphiphilic test compounds. Although quantitative differences exist between the different dihydropyridines, they are affected in potency by other compounds with a rather similar pattern. Accordingly, some general predictions about the interactions of a given dihydropyridine might be possible using limited datasets.
Schröder
F
F
Department of Pharmacology, University of Kiel, Fed. Rep. of Germany.
Herzig
S
S
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002412:Cations / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects
D002121:Calcium Channel Blockers; D002412:Cations; D004095:Dihydropyridines