Disease relevance of fendiline

• 3 The anti-ischaemic effect of fendiline is mainly due to its negative chronotropic action, whereas that of verapamil is due in part to bradycardia and in part to the reduced preload and afterload [1].
• BACKGROUND: The effects of the anti-anginal drug fendiline on intracellular Ca2+ concentrations ([Ca2+]i) in human PC3 prostate cancer cells were examined [2].
• Effects of the antianginal drug fendiline on Ca2+ movement in hepatoma cells [3].
• In a 6-week, randomized, double-blind trial, the drug effects of the calcium antagonists, fendiline (75 mg twice daily) and diltiazem (90 mg twice daily), as measured by subjective and objective parameters of coronary heart disease, were studied in 79 patients with stable angina pectoris [4].
• In particular, in regard to electrophysiology, torsade de pointes are not expected to be induced by fendiline [5].

High impact information on fendiline

• The synthesis of EDRF/NO was inhibited by the following antagonists of calmodulin-regulated functions (with the approximate IC50 values given in parentheses): calmidazolium (7 microM), trifluoperazine (10 microM), fendiline (80 microM), W-7 (N-[6-aminohexyl]-5-chloro-1-naphthalenesulfonamide) (120 microM), and compound 48/80 (3 micrograms/ml) [6].
• BayK8644 (10 microM) also reversed the potency ratio of verapamil/fendiline in smooth muscle, with respect to changes in tension induced by K+ (48 mM) [7].
• Open state block by fendiline of L-type Ca++ channels in ventricular myocytes from rat heart [7].
• The IC50 of fendiline was 17.0 +/- 2.43 microM and the Hill slope was 1.39 +/- 0.23 [8].
• 4. Fendiline inhibited ICa at all the membrane potentials tested and shifted the current-voltage curve upwards [8].

Chemical compound and disease context of fendiline

• Effect of Sensit (fendiline) in angina pectoris [9].

Biological context of fendiline

• 2. Fendiline-induced block of ICa is accompanied by modulation of the channel kinetics in a complex manner [10].
• Together, the findings indicate that in BFTC cells, fendiline exerts a dual effect: mobilization of intracellular Ca2+ and induction of cell death [11].
• Fendiline (100 micromol/l) decreased cell viability by 12-44% after being added to cells for 2- 30 min [11].
• Frequency- and time-dependent effects of fendiline on action potentials of guinea pig papillary muscle [12].
• Blood pressure and heart rate were clearly lowered by diltiazem, whereas fendiline induced only a slight decrease in blood pressure [4].

Anatomical context of fendiline

• 1. The effects of the calmodulin antagonists, calmidazolium and fendiline were investigated on endothelium-dependent hyperpolarization in the canine coronary artery [13].
• In Ca2+-free medium, pretreatment with 100 microM fendiline inhibited most of the [Ca2+]i increase induced by 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), and pretreatment with thapsigargin abolished the fendiline-induced [Ca2+]i increases [2].
• Calmidazolium and fendiline were also applied to endothelial cells loaded with the fluorescent indicator of free calcium concentration (Ca2i+), indo-1 [14].
• In addition they provide further evidence for effects other than at the cell membrane which could theoretically contribute to the efficacy of bepridil and fendiline as anti-anginal agents [15].
• The anti-anginal drug fendiline elevates cytosolic Ca(2+) in rabbit corneal epithelial cells [16].

Associations of fendiline with other chemical compounds

• Comparison of two calcium antagonists, verapamil and fendiline, in an experimental model of myocardial ischaemia mimicking classical angina on effort [1].
• Kinetic modulation of guinea-pig cardiac L-type calcium channels by fendiline and reversal of the effects of Bay K 8644 [10].
• Novel, 2'-hydroxy derivatives of fendiline have been synthesised and their ability to induce relaxation of isolated rat small mesenteric and coronary arteries were determined [17].
• In contrast, basic pharmacology reveals major differences of the actions of prenylamine and fendiline in heart muscle, indicating that, after all, the change in structure close to the asymmetric carbon strongly influences the molecular action of the compounds and their respective isomers [5].
• Enhancement of the cytogenetic efficacy of the antitumor agent bleomycin by the calcium and calmodulin antagonist fendiline [18].

Gene context of fendiline

• Fendiline is more active against the oxytocin-induced contraction, probably due to an additional action on the fast Na+ channels [19].
• Intracellular localization of the calcium- and calmodulin antagonist fendiline [20].
• In this review, we present a new class of phenylalkylamines, based on the lead compound fendiline, that are potent positive potentiators of GABAB receptor-mediated function and discuss their putative clinical applications [21].

Analytical, diagnostic and therapeutic context of fendiline

• The effects of fendiline on L-type Ca++ currents [ICa(L)] were investigated in rat ventricular cardiomyocytes using the patch-clamp technique both in the whole-cell disrupted-patch and in the cell-attached configuration [7].
• Determination of fendiline in human plasma by means of capillary gas chromatography and nitrogen-phosphorus selective detection [22].
• Capillary isotachophoresis was applied for the determination of fendiline and gallopamil--calcium antagonists--in serum [23].
• By adding calcium to the medium, almost all types of muscle activation are established, after the inhibitory action of fendiline, except its depressive action on the electrical stimulation of the isolated rat uterus [19].
• Fendiline was administered intravenously (3 mg) and orally (50 mg and 75 mg) in a cross-over study to six healthy volunteers [24].

References