Disease relevance of R 56865

• Myocytes were also exposed to hypoxia in the presence of R 56865, a compound that blocks noninactivating components of the Na+ current [1].
• We conclude that R 56865 delays the onset of cellular uncoupling during ischemia and that this effect is not related to changes of conduction velocity and at most in part to changes of APD80 [2].
• 1. In isolated cardiac muscle, submicromolar concentrations of R 56865 (N-[1-[4-(4-fluorophenoxy)-butyl]-4-piperidinyl]-N-methyl-2- benzothiazolamine) have been shown to attenuate the toxicity of cardiac glycosides [3].
• Mechanical signs of intoxication, e.g. extrasystoles and contracture, as well as the development of spike-like action potentials could be prevented by pretreatment with R 56865 (3 X 10(-10)-10(-6) mol/l) [4].
• No significant differences were observed between placebo and R 56865 (20 mg) concerning time to onset and duration of ST-segment changes and symptomatic angina pectoris, respectively [5].

High impact information on R 56865

• In this way, R 56865 may contribute to prevention of action potential shortening and inhomogeneous repolarisation.(ABSTRACT TRUNCATED AT 250 WORDS)[6]
• Experiments were performed with isolated perfused rabbit papillary muscles that were treated with 1 microM R 56865 for 45 min prior to ischemia [2].
• To verify intoxication with ouabain as an experimental model for ischaemic/hypoxic insults, the effect of an investigational drug with antiischaemic/hypoxic properties (R 56865) was evaluated in the model [7].
• Secondly, flunarizine and R 56865 seemed to evoke their effects by interfering with the permeability of Na+ channels [8].
• The effect of the anti-ischemic compounds flunarizine and R 56865 on the veratridine-induced uptake of Ca2+ and Na+ was observed in cortical synaptosomes in the rat [8].

Chemical compound and disease context of R 56865

• Ouabain-induced changes of calcium and potassium in slices of hippocampus of the rat: comparison to hypoxia and effect of R 56865 [7].
• These results demonstrate that R 56865 reverses cardiac glycoside-induced arrhythmias in anesthetized dogs at doses that do not significantly affect conduction or refractoriness [9].

Biological context of R 56865

• When pretreated with R 56865, the occurrence of afterdepolarizations was prevented and the decline of the resting membrane potential was attenuated [3].
• Flunarizine and R 56865 suppress veratridine-induced increase in oxygen consumption and uptake of 45Ca2+ in rat cortical synaptosomes [8].
• Effects of R 56865 on postischemic ventricular function in isolated rat working heart preparations obtained from healthy, diabetic and hypertensive animals [10].
• It clearly demonstrates that the potent cardioprotective properties of R 56865 are unrelated to intracellular sodium homeostasis [11].
• The positive inotropism induced by ouabain was not impaired by R 56865 [4].

Anatomical context of R 56865

• R 56865 delays cellular electrical uncoupling in ischemic rabbit papillary muscle [2].
• The present study was designed to evaluate the potential anti-ischaemic activity of R 56865 in patients with coronary artery disease, scheduled to undergo percutaneous transluminal coronary angioplasty (PTCA) [5].
• R 56865 had no effect on normal automaticity in canine Purkinje fibers at 1 microM, but 10 microM significantly slowed it [9].
• Although the mechanism of the antiarrhythmic effects of R 56865 remains to be determined, we speculate that the drug raises the threshold for both generation of triggered action potentials and calcium-induced calcium release from the sarcoplasmic reticulum [12].
• Effects of R-56865 on transient inward current, Na(+)-Ca2+ exchange, and Ca2+ release from SR in cardiac myocytes [13].

Gene context of R 56865

• KC 12291 and R 56865 dose-dependently induced bradycardia (Delta heart rate obtained, -55.1+/-5.2 beat per min, P<0.05, and -71.9+/-8.5 bpm, P<0.05, respectively) [14].
• The AVP-induced contraction was not affected by R 56865 (10(-5) mol/l) [15].

Analytical, diagnostic and therapeutic context of R 56865

• During ischemia, conduction velocity was statistically not different between the R 56865 group and the control group [2].
• The negative inotropic and chronotropic effects of intravenous R 56865 during percutaneous transluminal coronary angioplasty [5].
• After 15 min of pretreatment with R 56865, low-flow ischemia (30 min) was induced by reducing the perfusion pressure from 51.5 mmHg to 11.0 mmHg and R 56865 was infused simultaneously [10].
• R 56865, a cytoprotective agent, has been shown to prevent myocardial ischemia and reperfusion injury by blockade of the late sodium current (I(Nal)) [16].
• The effect of R 56865 on I(Nal) in isolated human atrial myocytes was investigated by using the whole-cell patch-clamp technique [16].

References