3,5-dibenzoyl-4-(3-phenoxyphenyl)-1,4-dihydro-2,6-dimethylpyridine (DP7): a new multidrug resistance inhibitor devoid of effects on Langendorff-perfused rat heart.
Cardiac effects of 3,5-dibenzoyl-4-(3-phenoxyphenyl)-1,4-dihydro-2,6-dimethylpyridine (DP7), a novel multidrug resistance (MDR) inhibitor, in Langendorff-perfused rat heart have been investigated and compared to that of nifedipine. Nifedipine decreased concentration-dependently (IC50=8.89+/-1.09x10(-8) M) left ventricular pressure leaving unaltered coronary perfusion pressure, whereas DP7 did not affect both parameters. Nifedipine did not modify both QRS and QT intervals of electrocardiogram (ECG). Second-degree atrioventricular block or ventricular rhythm occurred in presence of nifedipine, however, in 4 out of 6 hearts. DP7, up to 30 microM, failed to alter ECG parameters. In conclusion, DP7, may represent a lead compound for the development of potent dihydropyridine MDR chemosensitizers devoid of cardiac effects.
Saponara
Simona
S
Dipartimento di Scienze Biomediche, Università degli Studi di Siena, via A. Moro 2, 53100 Siena, Italy.
Ferrara
Antonella
A
Gorelli
Beatrice
B
Shah
Anamik
A
Kawase
Masami
M
Motohashi
Noboru
N
Molnar
Joseph
J
Sgaragli
Giampietro
G
Fusi
Fabio
F
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology*; D004095:Dihydropyridines / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000009:adverse effects / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
C492000:3,5-dibenzoyl-4-(3-phenoxyphenyl)-1,4-dihydro-2,6-dimethylpyridine; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009543:Nifedipine