The aim of this study was to evaluate the effect of anipamil, a phenyalkylamine-derived Ca(2+)-antagonist, on aortic intimal thickening and smooth muscle cell (SMC) phenotype in 2K-1C hypertensive rabbits. Monoclonal antimyosin antibodies [SM-E7, NM-G2, and NM-F6, which respectively, recognize smooth muscle (SM), A-type-, and B-type-like nonmuscle (NM) myosin heavy chains (MyHC)] identify different aortic SMC types: adult (SM-E7-positive), postnatal (SM-E7- and NM-G2-positive), and fetal (SM-E7-, NM-G2-, and NM-F6-positive). Twenty-four hypertensive rabbits were studied 2.5 months (n = 12) and 4 months (n = 12) after clipping. Six animals from each group were given anipamil (40 mg orally, once daily) immediately after surgery. The remaining 2K-1C were given a daily oral placebo. Normotensive age-matched controls were also studied. Transverse cryosections of aorta were taken for computerized morphometry and immunocytochemical studies. Primary and secondary SMC cultures were used to define potential changes in cell phenotype after adding anipamil to the culture medium. In untreated 2K-1C, intimal thickening, mainly composed of postnatal-type SMC, was found by 2.5 months after clipping. Morphometric and immunofluorescence studies in anipamil-treated 2K-1C rabbits revealed absent or negligible intimal thickening and a decrease of postnatal-type SMC from the underlying media. In culture experiments, growth inhibition of SMC by anipamil was accompanied by the expression of SM-MyHC in all SMC, ie, the appearance of a more differentiated cell phenotype compared to control cultures. In conclusion, prevention of intimal thickening in anipamil-treated 2K-1C was achieved through selective reduction in the media of the postnatal-type SMC. This could be achieved by reducing NM-MyHC content or increasing synthesis of SM-MyHC expression. As blood pressure was not significantly lowered by anipamil treatment, a direct and specific antiproliferative action of this drug on medial SMC is likely to take place.

01 Sep 1995·Journal of Cardiovascular PharmacologyQ4 · MEDICINE

(–)-Anipamil Retards Atherosclerosis in Watanabe Heritable Hyperlipidemic Rabbits

Q4 · MEDICINE

Article

Author: Hansen, Birgit Fischer ; Mortensen, Alicja ; Frandsen, Henrik ; Hansen, Joergen Fischer

Calcium antagonists have been reported to limit atherosclerosis in cholesterol fed rabbits. The purpose of this study was to examine the effect of the calcium antagonist (-)-anipamil on the spontaneous development of atherosclerosis in homozygote WHHL rabbits. From the age of 7 weeks, three groups of rabbits received 0 (control, n = 11), 1 mg/kg body weight (n = 11), or 10 mg/kg body weight (n = 12) of (-)-anipamil for 17 weeks. Serum cholesterol at start of the investigation was 18.8 +/- 1.2 (mean +/- SEM), 20.5 +/- 1.8, and 19.5 +/- 0.8 mM, respectively, in the three groups. No significant differences were found in serum lipids (i.e., VLDL, IDL, LDL, HDL) in the study period among the three groups. Plasma anipamil at the end of the study was 0.23 +/- 6, and 202 +/- 19 ng/ml, respectively, in the three treatment groups. The degree of atherosclerosis in the abdominal aorta was significantly lower (p < 0.02) in the 10 mg/kg body weight (-)-anipamil group compared with the two other groups. No significant difference was found in the thoracic aorta. It is concluded that (-)-anipamil retards development of atherosclerosis in the abdominal aorta in WHHL rabbits.

01 Aug 1995·Life SciencesQ3 · MEDICINE

Effects of anipamil, a long acting analog of verapamil, in pigs subjected to myocardial ischemia

Q3 · MEDICINE

Article

Author: C.R. Ries ; L.J. Guppy ; M.K. Pugsley ; C.J. Harvie ; M.J.A. Walker

In this study we examined the cardiovascular and possible antiarrhythmic actions of anipamil, a long acting analog of verapamil. Initial dose-response studies for anipamil (0.25-6.0 mg/kg, i.v.) in pentobarbitone-anesthetized pigs (n = 4) were conducted to determine the effects of the drug on EKG and hemodynamic measures. In this initial study anipamil was found to produce a dose-dependent reduction in blood pressure, left-ventricular pressure and its derivative (dP/dtmax), cardiac output, and increase in heart rate. These results were used as a basis from which to choose doses for a second study to assess antiarrhythmic actions of anipamil against arrhythmias induced by regional myocardial ischemia. The antiarrhythmic effects of the two doses were compared with verapamil when the latter was given at a dose producing cardiovascular effects mid-way between those produced by the two doses of anipamil. Anesthetized pigs were randomly assigned to receive one of three drug treatments, or vehicle control, prior to occlusion of the left-anterior descending coronary artery. Antiarrhythmic effectiveness of low (1.0 mg/kg + 0.10 mg/kg/min infusion, n = 8) and high (5.0 mg/kg + 0.50 mg/kg/min infusion, n = 12) dose anipamil was compared to that of verapamil (0.5 mg/kg + 0.60 mg/kg/min infusion, n = 8) in a vehicle controlled study (n = 15). Arrhythmic events (VPB, VT and VF incidence) were monitored and grouped according to their time of occurrence after occlusion. Thus phase 1a arrhythmias occurred 0-5 min after initiation of occlusion, phase 1b, 5-30 min, and phase 2, 0.5-4 hr after occlusion. This study showed that during phase 1a there was a low incidence of arrhythmias in all groups except the one receiving 5 mg/kg anipamil where the group incidence of VT was 58% as compared to 20% in controls (n = 15). Most ventricular arrhythmias occurred in all groups during phase 1b. In this phase verapamil abolished VF and reduced VT, as compared with controls. Anipamil (high and low doses) tended to reduce VT but not VF. In the period 0.5 to 4 hours post occlusion (phase 2) all three drug treatments were associated with fewer arrhythmias but this only reached statistical significance with verapamil. Thus verapamil was more efficacious than anipamil at providing antiarrhythmic protection against both early and late onset arrhythmias. Anipamil may have been proarrhythmic in the early phase of arrhythmias and only moderately antiarrhythmic, if at all, in the later phase.(ABSTRACT TRUNCATED AT 400 WORDS)

100 Deals associated with Anipamil

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KEGG	Wiki	ATC	Drug Bank
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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Atherosclerosis	Phase 3	-	AbbVie, Inc.	-
Hypertension	Phase 3	-	AbbVie, Inc.	-
Hypertension	Phase 3	AT	-	-
Hypertension	Phase 3	DE	Abbott Laboratories	-
Myocardial Ischemia	Phase 3	-	AbbVie, Inc.	-
Myocardial Ischemia	Phase 3	UG	-	-

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