Flunarizine, (E)-1 -[bis(4-fluorophenyl)methyl]-4-( 3-phenyl-2-propenyl) piperazine ( Fig. 1), belongs to the chemically heterogenous group of calcium-entry blockers (16,101,113). Chronic treatment with flunarizine provides symptomatic relief of peripheral (arterial and venous) and cerebral circulatory disorders (23,27,31,50,(52)(53)(54)59,60,72,80,81,(83)(84)(85)(86)92,93,120,133). The drug is also used for the treatment of vestibular disorders (12,52,65,128) and may be beneficial in the prophylactic treatment of migraine (1,2,26,29,63,64,82). Ongoing studies have demonstrated the effectiveness of this compound in therapy-resistant forms of epilepsy ( 17,74). The suggestion has been made that flunarizine may be helpful in some cases of urinary incontinence (75,87). The therapeutic effects may be due, at least in part, to its ability to inhibit the entry of calcium ions (Ca2+) into tissue cells, thereby preventing cellular intoxication due to an overload of Ca2+ (15,113). In particular, the compound affects the function of vascular smooth muscle cells, endothelial cells, myocardial cells, erythrocytes, and brain cells (13,15,16,35,36,76,103,104,114). F FIG. 1. Three-dimensional representation of the chemical structure of flunarizine based on the crystal structure conformation of cinnarizine (J. Tollenaere and H. Moereels, unpublished data). 245 246 120 ~ 100z I-2 80-V < n t 60-I 1 I I 8 I I -15 -10 -5 0 5 10 20 30 $0 50 60 70 80 90 MIN FIG. 2. Depression of K+-induced contractions of canine basilar arteries by increasing concentrations (M) of flunarizine. Means 5 SE; N = 5.