In order to prevent and treat angioplasty-induced vasospasm, we investigated the effects of a new Ca2+ channel antagonist, fantofarone, a nondihydropyridine compound with a novel site of action on the L-type Ca2+ channel, in an animal model of angioplasty in rabbits with femoral atherosclerotic lesions. Vasospasm which occurred in saline-treated animals following angioplasty was markedly reduced by fantofarone (50 microg/kg, i.v.) at both the distal and proximal sites. Although it totally inhibited distal vasospasm, isosorbide dinitrate (0.3 mg/kg, i.v.) did not significantly affect proximal diameter decrease. Verapamil (0.2 mg/kg, i.v.) was much less potent than fantofarone in reducing angioplasty-induced vasospasm. Our results confirm the preventive effects of Ca2+ blockers on this phenomenon and extend this observation to a potent compound: fantofarone.