Animal experiment:

Preliminary studies are performed to determine the anipamil dose response. Anipamil is mixed with food to give a dose of 0.5, 2 or 5 mg/kg/day. One week after five-sixths nephrectomy, rats are paired according to renal function, blood pressure and body weight. Rats are then pair-fed and receive either the long-acting calcium channel blocker anipamil (2 mg/kg/day in food, n=20) or placebo (n=20).

Anipamil is a long-acting calcium channel blocker, used for the treatment of cardiovascular disease.

Anipamil (40 mg, p.o.)-treated 2K-1C rabbits reveal absent or negligible intimal thickening and a decrease of postnatal-type SMC from the underlying media. Anipamil inhibits the growth of SMC accompanied by the expression of SM-MyHC in all SMC, ie, the appearance of a more differentiated cell phenotype compared to control cultures[1]. In the arrhythmic assay, anipamil (1.0 mg/kg + 0.10 mg/kg/min infusion, n=8 or 5.0 mg/kg + 0.50 mg/kg/min infusion, n=12) reduces VT but not VF[2]. In rats with subtotal (five-sixths) nephrectomy treated with anipamil (0.5 mg/kg/day, p.o.), the mortality is less, and the mean arterial blood pressure is also more well controlled, and the serum creatinine concentration is lower than control group. The anipamil (2 mg/kg/day)-treated group exhibits significantly greater protection of renal function than does the hydralazine-treated group for the same level of blood pressure control[3].

[1]. Pauletto P, et al. Anipamil prevents intimal thickening in the aorta of hypertensive rabbits through changes in smooth muscle cell phenotype. Am J Hypertens. 1996 Jul;9(7):687-94. [2]. Pugsley MK, et al. Effects of anipamil, a long acting analog of verapamil, in pigs subjected to myocardial ischemia. Life Sci. 1995;57(12):1219-31. [3]. Jarusiripipat C, et al. Effect of long-acting calcium entry blocker (anipamil) on blood pressure, renal function and survival of uremic rats. J Pharmacol Exp Ther. 1992 Jan;260(1):243-7.