Effect of calcium inhibitors and calcium mobilizers on doxorubicin accumulation in rat myocardial tissue.
The effect of four calcium-modulating agents on myocardial doxorubicin (DXR) accumulation was studied: the calcium-inhibitors verapamil (0.1 microM), trifluoperazine (5 microM) and flunarizine (0.05 microM) and the calcium-mobilizer taurine (50 mM). Myocardial cells of isolated Langendorff rat hearts receiving the drugs showed a significantly enhanced 14C-DXR uptake. These observations are in contrast with the hypothesis that DXR accumulation processes may be related to a decrease in calcium influx and suggest that a combined therapy with DXR and calcium-modulating agents might enhance the drug-induced cardiotoxicity.
Cattedra di Farmacologia Applicata, Università di Milano.
E
E
Monti
L
L
Paracchini
F
F
Piccinini
A
A
Rozza
F
F
Villani
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004317:Doxorubicin / Q000378:metabolism*; D005444:Flunarizine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D013654:Taurine / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D013654:Taurine; D014268:Trifluoperazine; D004317:Doxorubicin; D014700:Verapamil; D005444:Flunarizine; D002118:Calcium