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At least 19 recordsLinked to original sources

PubMed1987

Does if control normal automatic rate in canine cardiac Purkinje fibers? Studies on the negative chronotropic effects of lidoflazine.

Lidoflazine has been reported to decrease the conductance of the slow inward current and of the pacemaker current (if) in cardiac tissues. We studied the effects of lidoflazine on normal and abnormal automaticity in isolated preparations of canine and ovine cardiac Purkinje fibers. Normal automaticity occurred in fibers with maximum diastolic potentials (MDPs) greater than -85 mV, and abnormal automaticity occurred in fibers with MDPs less than -60 mV. Normal automaticity was studied in fibers superfused with Tyrode's solution containing 2.7 mM KCl, 4 mM KCl, 4 mM KCl with 1 microM isoproterenol (ISO), and 4 mM KCl with 25 microM BaCl2. In each experiment, normal automatic rate was stable for at least 30 min before lidoflazine was added to the superfusate; lidoflazine did not decrease the rates significantly in any of the four series of experiments. However, when fibers with normal MDPs were pretreated with lidoflazine, the drug blunted the increase in rate that occurred 12-15 min after the start of exposure to ISO. However, lidoflazine significantly decreased abnormal automaticity induced by barium (250 microM or 5 mM). The results indicate that normal automaticity in Purkinje fibers is not affected by lidoflazine and is probably not controlled by if. Rather, normal rate is controlled by the magnitude of background potassium conductance (gK), as indicated by the significant effects of barium (25 microM) on rate. Lidoflazine may blunt the effects of ISO on rate by inhibiting if, but after ISO rhythms are established, they are probably maintained by triggered impulses that are not affected by lidoflazine. Lidoflazine may slow abnormal automaticity by inhibition of the slow inward current.

Action Potentials↗

PubMed1992

Nucleoside transport inhibition mediates lidoflazine-induced cardioprotection during intermittent aortic crossclamping.

The effects of pretreatment with the nucleoside transport inhibitor lidoflazine on repeated ischemia-reperfusion injury induced by normothermic intermittent aortic crossclamping were studied in canine hearts. Eighteen mongrel dogs were allocated to three groups: placebo (n = 6), lidoflazine (1 mg/kg) (n = 6), and lidoflazine (1 mg/kg) plus the adenosine receptor blocker aminophylline (7 mg/kg) (n = 6). Pretreatment was performed intravenously during 15 minutes before extracorporeal circulation. All hearts were subjected to four intervals of 15 minutes of global ischemia each followed by 10 minutes of reperfusion. After weaning from extracorporeal circulation, functional recovery was followed for 1 hour. In the lidoflazine group, myocardial adenosine content (0.25 +/- 0.06 mumol/gm dry weight) was 3.5 times higher than that in the control group (0.07 +/- 0.03 mumol/gm dry weight; p < 0.05) at the end of the last aortic crossclamping. The release of adenosine from the myocardium during each reperfusion period was significantly higher than that in the control group (p < 0.05). Myocardial extraction of lactate was normalized at every reperfusion interval in the lidoflazine group but not in the control group (p < 0.05). In the lidoflazine group functional recovery was significantly better than that in the control group. Positive rate of rise of pressure, negative rate of rise of pressure, and cardiac output recovered to, respectively, 150% +/- 19%, 82% +/- 8%, and 131% +/- 15% in the lidoflazine group versus, respectively, 37% +/- 9%, 23% +/- 7%, and 29% +/- 8% in the control group (p < 0.001) at 1 hour after extracorporeal circulation. When the adenosine receptor blocker aminophylline was administered in association with lidoflazine, protection dropped significantly: positive and negative rate of rise of pressure and cardiac output were, respectively, 58% +/- 8%, 46% +/- 9%, and 67% +/- 16% at 1 hour after extracorporeal circulation (p < 0.05 versus lidoflazine alone). These results suggest that the cardioprotective effects of lidoflazine are at least in part mediated by adenosine receptor stimulation via nucleoside transport inhibition-induced accumulation of endogenous adenosine in the myocardium.

Adenosine↗

PubMed1990

Beneficial and detrimental effects of lidoflazine in microvascular angina.

Lidoflazine, a piperazine derivative calcium antagonist, was investigated as therapy in 22 patients with microvascular angina (chest pain, angiographically normal coronary arteries and left ventricle, microvascular constrictor response to pacing after ergonovine administration and limited coronary flow response to dipyridamole). Eighteen of 22 patients reported symptom benefit while taking lidoflazine 360 mg daily. Compared to baseline exercise treadmill testing, lidoflazine resulted in significant improvement in exercise duration (812 +/- 337 vs 628 +/- 357 seconds, p less than 0.01) and time to onset of chest pain (530 +/- 343 vs 348 +/- 246 seconds, p less than 0.01). The 5 patients with ischemic ST-segment changes during baseline testing demonstrated an almost 4-minute delay in ST-segment depression (3 patients) or no ST-segment depression (2 patients) while taking lidoflazine. Repeat invasive study of coronary flow in 11 patients taking lidoflazine demonstrated significantly greater coronary vasodilation at rest, during pacing, during pacing after ergonovine and after dipyridamole administration (all p less than 0.03), compared to the initial drug-free study. During the randomized, placebo-controlled phase of the study with 7-week treatment periods, 9 of 11 patients who completed this phase of the study preferred lidoflazine and all demonstrated improved exercise capacity with lidoflazine compared to placebo. However, 3 patients developed malignant ventricular arrhythmias, and 1 died while taking lidoflazine, resulting in termination of the study. Limited coronary vasodilator response in microvascular angina has a reversible vasoconstrictor component and may be due to elevated systolic calcium levels. Despite the hemodynamic, symptom and exercise benefit, lidoflazine may be unsafe for clinical use because of its propensity to cause potentially fatal ventricular arrhythmias.

Adult↗

PubMed1984

Studies on the possible mechanisms of lidoflazine arrhythmogenicity.

Lidoflazine is a calcium channel blocking agent that is effective and safe in the treatment of angina pectoris, but has been reported to be associated with sudden death when administered for the treatment of supraventricular arrhythmias. Studies were performed in dogs to determine if lidoflazine caused a rise in serum digoxin concentration that could cause arrhythmias or if it was directly arrhythmogenic. Dogs received chronic injections of digoxin and then digoxin in combination with lidoflazine. No increase in digoxin concentration was found. Dogs also underwent programmed electrical stimulation while not receiving medications and then after incremental doses of lidoflazine administered intravenously. Lidoflazine did not cause spontaneous ventricular tachycardia and did not lower the threshold of ventricular tachycardia induction. Combined administration of lidoflazine and digoxin did not facilitate arrhythmia induction. These studies do not support a digoxin-lidoflazine interaction or a direct arrhythmogenic action of lidoflazine.

Animals↗

PubMed1988

Relaxing effects of dilazep and lidoflazine in dog cerebral and renal arteries independent of adenosine.

The adenosine potentiating drugs dilazep and lidoflazine were studied for their relaxing ability in isolated dog cerebral and renal arteries contracted under conditions which induce the opening of potential-dependent calcium channels (using K+ at 30, 50 and 100 mmol/l) and under conditions which induce the opening of receptor-operated calcium channels (prostaglandin F2 alpha, PGF2 alpha; 5-hydroxytryptamine, 5-HT) and compared with those of adenosine and a standard calcium entry blocker, diltiazem. Dilazep, lidoflazine and diltiazem exerted concentration-dependent relaxation in cerebral and renal artery ring strips contracted with 30, 50 and 100 mmol/l K+. However, dilazep was slightly more potent at 100 mmol/l K+. In contrast, whereas the high concentration of adenosine (1 X 10(-5)-3.7 X 10(-4) mol/l) relaxes these arteries only at 30 mmol/l K+, it produced a more pronounced concentration-dependent relaxation when PGF2 alpha or 5-HT was used as a contracting agent. The order of relaxing responses of both cerebral and renal arterial ring strips contracted by PGF2 alpha were: diltiazem greater than adenosine greater than lidoflazine greater than dilazep. On the other hand, the relaxing responses on cerebral and renal arteries contracted with 5-HT were: diltiazem greater than lidoflazine greater than adenosine greater than dilazep and diltiazem greater than adenosine greater than lidoflazine greater than dilazep, respectively. Adenosine deaminase reversed the relaxation produced by adenosine, but was unable to reverse the relaxing responses to diltiazem, lidoflazine and dilazep. These findings suggest that dilazep and lidoflazine have a direct relaxing effect independent of adenosine in cerebral and renal artery ring strips possibly through their calcium entry blocking activity. The data suggest that adenosine is more effective on the receptor-operated contractions, whereas dilazep and lidoflazine are more effective on the potential-dependent contractions.

Adenosine↗

PubMed1980

Inhibitory effect of lidoflazine on contractions of isolated canine coronary arteries caused by norepinephrine, 5-hydroxytryptamine, high potassium, anoxia and ergonovine maleate.

Experiments were performed on isolated coronary arteries to determine whether or not lidoflazine, an agent reported to be beneficial in the treatment of angina pectoris, is effective in antagonizing coronary vasoconstriction. Segments of canine circumflex and right coronary arteries were suspended in organ chambers filled with aerated Krebs-Henseleit solution (37 degrees C) for continuous isometric tension recordings. Dose-dependent contractions were obtained with norepinephrine (in presence of propranolol) and 5-hydroxytryptamine; these contractile responses were antagonized by phentolamine and methysergide, respectively. Lidoflazine caused long-lasting, and dose-dependent inhibition of the responses to both norepinephrine and 5-hydroxytryptamine. High K+ solution (30 mM) caused sustained contraction of the coronary segments; these responses were depressed in a dose-dependent manner by lidoflazine. Lidoflazine slightly augmented relaxations caused by adenosine. Addition of Ca++ to the bath solution partially reversed the inhibitory effect of lidoflazine, which indicates that the compounds acts by inhibiting the influx of extracellular Ca++. Segments incubated in solution containing 20 mM K+ and subjected to anoxia exhibited transient contractions which were inhibited by lidoflazine. Ergonovine maleate caused contractures of the coronary arteries which also were antagonized in a dose-dependent manner by lidoflazine. These experiments demonstrate the ability of lidoflazine to counteract contractions of coronary vascular smooth muscles caused by factors which may be involved in the etiology of coronary vasospasm.

Animals↗

PubMed1979

Lidoflazine in the management of angina pectoris.

The effect of lidoflazine administration (120 mg t.i.d. for 9 weeks) on work tolerance (bicycle ergometer), frequency of anginal attacks, and nitroglycerin consumption was investigated in 28 male patients with stable angina pectoris in a combined single-blind/double-bline study. Lidoflazine increased work tolerance and reduced the frequency of anginal attacks and nitroglycerin consumption. The higher work tolerance level was reached at maximal heart rate and heart rate--systolic blood pressure product values similar to those before treatment. The values of these variables after 3 min of exercise at 60 W, however, were significantly lower after treatment with lidoflazine. These findings indicate that the heart is performing more economically during lidoflazine treatment. The improved work tolerance can probably be ascribed to lidoflazine and not to a training effect because of the significant reduction of this variable in the patients allocated to placebo as compared to those remaining on lidoflazine treatment. The side effects were generally slight. In one patient the prolongation of the QT interval due to lidoflazine resulted in rhythm disturbances.

Adult↗

PubMed1992

Improvement of renal preservation by adding lidoflazine to University of Wisconsin solution. An experimental study in the rat.

The purpose of this study was to investigate the possibility of improving the organ preservation properties of the University of Wisconsin (UW) solution by adding the calcium entry blocker lidoflazine. We also investigated the possibility of decreasing the cold ischemia and reperfusion damage by pretreatment with lidoflazine of the donor and/or recipient. The protective effects of lidoflazine treatment were estimated by measuring the amount of trapped erythrocytes in the rat renal medulla after 48 h of cold storage, subsequent transplantation, and 20 min of reperfusion. Lidoflazine (20 mg/liter) added to the UW solution decreased the amount of erythrocyte trapping from 14.8 +/- 3.1% in controls to 8.6 +/- 1.7% (P less than 0.01). The flow rate of the flush-out solution during the harvesting procedure was also significantly (P less than 0.01) increased when lidoflazine was included in the UW solution (1.10 +/- 0.21 ml/min vs 0.75 +/- 0.22 ml/min). Administration of lidoflazine (0.28 mg/kg body wt) to the donor and/or the recipient did not further reduce the postischemia/reperfusion damage as estimated by the degree of erythrocyte trapping. In conclusion, the results indicate that the preservation properties of the UW solution can be significantly improved by adding lidoflazine to the solution.

Adenosine↗

PubMed1984

An analysis of the rate-dependent action of lidoflazine in mammalian sino-atrial node and Purkinje fibres.

Lidoflazine is an anti-anginal drug whose beneficial effect is to reduce the heart rate increment on exercise. Micro-electrode recording was performed in the spontaneously-beating, isolated guinea-pig sino-atrial node. It was shown that low concentrations (less than 5 X 10(-6) M) of lidoflazine alone did not alter action potential configuration or beating frequency. However, the drug reduced the spontaneous rate and the slope of the diastolic depolarization in the presence of catecholamine. This effect of lidoflazine was more pronounced at higher catecholamine concentrations. The action of lidoflazine on the hyperpolarization-activated current if was studied using a 2-micro-electrode voltage-clamp technique on shortened sheep Purkinje fibres. The activation curve for if was not affected by the drug. The slope of the fully-activated current-voltage relation was reduced by a mean of 20.1% on exposure to 5 X 10(-6) M lidoflazine. Using a computer model of Purkinje fibre action potentials, the observed reduction in maximal if conductance was shown to account quantitatively for the effects of lidoflazine. It is proposed that lidoflazine slows the heart by reducing the conductance of the if channel. This may be brought about by a fall in intracellular calcium concentration.

Action Potentials↗

PubMed1987

Lidoflazine does not improve neurologic outcome when administered after complete cerebral ischemia in primates.

In order to investigate the effects of the calcium entry blocker lidoflazine on neurologic outcome in primates following an episode of global brain ischemia, 12 pigtail monkeys (Macaca nemestrina) were subjected to 17 min of complete cerebral ischemia, followed by 48 h of intensive care treatment and daily neurologic evaluations for 96 h. The monkeys were randomly assigned to receive, in a blind fashion, either lidoflazine 1.0 mg/kg (n = 6) or inactive lidoflazine solvent (n = 6) at 5 min, 8 h, and 16 h postischemia. One monkey in the lidoflazine group did not meet preestablished protocol criteria and was excluded from data analysis. The remaining monkeys were well matched for age, sex, and other physiologic variables. Neurologic outcome was not significantly different between the lidoflazine- and placebo-treated groups (p greater than 0.5). No monkey in either group achieved a normal neurologic exam by 96 h postischemia. Three lidoflazine-treated monkeys and two placebo-treated monkeys died prior to the 96-h neurologic evaluation. These deaths were judged to be neurologic in origin. The authors concluded that lidoflazine does not improve neurologic outcome in primates when administered after 17 min of complete cerebral ischemia.

Animals↗

PubMed1984

Amelioration of brain damage by lidoflazine after prolonged ventricular fibrillation cardiac arrest in dogs.

Calcium entry blockers can ameliorate postischemic cerebral hypoperfusion, protect the myocardium against ischemia, and may protect against early postischemic neurologic deficit. This study documents that a calcium entry blocker, given after cardiac arrest, can ameliorate late postischemic neurologic deficit (ND). Thirty-four dogs received 10 min of ventricular fibrillation, restoration of spontaneous circulation by external cardiopulmonary resuscitation, and standard postarrest intensive care. Eleven of these dogs were given lidoflazine, 1 mg/kg body weight, within 10 min postarrest and again at 8 h and 16 h. Pupillary light reflexes, EEG activity, arterial-cerebrovenous oxygen gradients (O2 demand/supply ratios) and intracranial pressure were the same in both groups. After weaning from controlled ventilation at 24 h, ND scores improved consistently through the 96-h observation period in the lidoflazine-treated dogs. In the control group, ND scores were significantly higher than in the lidoflazine-treated dogs. In the lidoflazine-treated group, 5/11 dogs achieved normal overall performance and none remained comatose, whereas all control dogs had some deficit and 4/11 remained comatose. Delayed neurologic deterioration occurred in 6/11 control and 0/11 lidoflazine-treated dogs. Total mean cerebral histopathologic damage (HD) scores at 96 h were not significantly different between the two groups; however, individual HD scores and maximum cerebro-spinal fluid (brain-specific) creatine-phosphokinase activity--which increases after brain insults--correlated well with 96-h ND scores. In the lidoflazine group, life-threatening dysrhythmias were less frequent and the norepinephrine requirement for blood pressure maintenance was the same as in the control group. Cardiac output remained at prearrest levels in the lidoflazine-treated dogs, but decreased in the control group, particularly during the first 4 h postarrest.

Animals↗

PubMed1982

The effects of lidoflazine on exercise performance and thallium stress scintigraphy in patients with stable angina pectoris.

Lidoflazine is a synthetic drug with calcium-channel blocking effects. In a 7-month study, 36 patients with stable angina pectoris were tested during a 3-month single-blind placebo phase. Nineteen were then randomized by double-blind methods to lidoflazine and 17 to placebo therapy. The lidoflazine group had a significant (p less than 0.01) reduction in anginal attacks; the placebo group did not. Exercise testing demonstrated that lidoflazine therapy was associated with a 34% increase in total work performance and a 15.6% increase in peak calculated oxygen uptake during double-blind treatment (both p less than 0.004 compared with the placebo group). Heart rate was significantly reduced at submaximal levels of exercise during lidoflazine therapy (p less than 0.04). Nitroglycerin consumption and electrocardiographic changes at the end of exercise did not change during the double-blind phase. In a second study of six similar patients, single-blind administration of lidoflazine was associated with improved myocardial perfusion during exercise as determined by thallium-201 stress scintigraphy. These studies demonstrate that lidoflazine therapy is associated with relief of angina, an increased physical work capacity, and improved regional myocardial perfusion during exercise.

Angina Pectoris↗

PubMed1986

The effect of carbon dioxide, lidoflazine and deferoxamine upon long term survival following cardiorespiratory arrest in rats.

This study examined the effect of carbon dioxide, lidoflazine and deferoxamine therapy upon the 10-day survival incidence and subsequent neurologic function of rats subjected to 7 min of cardiorespiratory arrest with resuscitation. Cardiac arrest (asystole) was induced at time zero by injection of cold, 1% KCl into the left ventricle of ketamine-anesthetized rats pretreated with succinylcholine. Positive pressure ventilation was discontinued at time zero. Cardiopulmonary resuscitation (CPR) was begun at 7 min, and animals with return of spontaneous circulation were entered into the study. Twenty treated rats were ventilated for 1 h with 7% carbon dioxide-93% oxygen and given lidoflazine (2.0 mg/kg, i.v.) and deferoxamine (50 mg/kg, i.v.) 5 min after CPR. Twenty control rats were ventilated for 1 h with 100% oxygen and given lidoflazine vehicle and deferoxamine vehicle. Lidoflazine treatment (1.0 mg/kg) for the treated group, or lidoflazine vehicle for the control group, was repeated at 8 h postresuscitation. At 2 days postresuscitation, 75% of treated rats vs. 25% of control rats were alive (CHI2 = 10.0, d.f. = 1, P less than 0.01), and at 10 days, 60% of treated rats vs. 25% of control rats were alive (CHI2 = 5.01, d.f. = 1, P less than 0.05). There was no detectable neurologic deficit among survivors in either group at 15 days. The combination of carbon dioxide, lidoflazine and deferoxamine, administered after return of spontaneous circulation, is a simple and easily administered treatment regimen that improves the survival incidence without neurologic deficits in this animal model of cardiorespiratory arrest and CPR.

Animals↗

PubMed2004

Lidoflazine is a high affinity blocker of the HERG K(+)channel.

Lidoflazine is an antianginal calcium channel blocker that carries a significant risk of QT interval prolongation and ventricular arrhythmia. We investigated whether or not lidoflazine inhibits current through the rapid delayed rectifier K(+) channel alpha subunit (encoded by HERG - human ether-a-go-go-related gene), since this channel has been widely linked to drug-induced QT-prolongation. Lidoflazine inhibited potently HERG current (I(HERG)) recorded from HEK 293 cells stably expressing wild-type HERG (IC(50) of approximately 16 nM). It was approximately 13-fold more potent against HERG than was verapamil under similar conditions. On membrane depolarization, I(HERG) inhibition developed gradually, ruling out closed-channel state dependent inhibition. The effect of command voltage on the drug's action suggested that lidoflazine preferentially inhibits activated/open HERG channels. The S6 mutation Y652A largely eliminated the inhibitory action of lidoflazine, whilst the F656A mutation also reduced blocking potency. We conclude: first, that lidoflazine produces high affinity blockade of the alpha subunit of the HERG channel by binding to aromatic amino acid residues within the channel pore and, second, that this is likely to represent the molecular mechanism of QT interval prolongation by this drug.

Cell Line↗

PubMed1977

Comparison of lidoflazine and quindine in prophylactic treatment of arrhythmias.

The efficacy of quinidine versus lidoflazine therapy was compared in the maintenance of sinus rhythm after electrical cardioversion for atrial flutter or fibrillation in a group of 35 patients. Both quinidine and lidoflazine were relatively ineffective in maintaining sinus rhythm after cardioversion. Lidoflazine was also used to prevent supraventricular and ventricular tachycardias in a miscellaneous group of patients; one of these with paroxysmal supraventricular tachycardia developed runs of venttricular tachycardia soon after starting lidoflazine. The trial was stopped after 4 patients died while receiving lidoflazine, on the suspicion that their deaths may have been related to drug-induced arrhythmias. The arrhythmogenic potential of lidoflazine when used in patients with supraventricular arrhythmias constrasts with reports of its apparent safety in large numbers of patients with angina pectoris.

Adult↗

PubMed1985

Lidoflazine and propranolol combination treatment in chronic stable angina.

The short-term (1 month) and long-term (6 months) safety of combination lidoflazine-propranolol therapy was investigated in an open trial of 15 patients with stable angina of effort. The possible advantages of adding lidoflazine (titrated to 360 mg daily) to patients having a therapeutic response to propranolol (80-400 mg daily) was also evaluated. Effects on non-invasive indexes of left ventricular function (echocardiography, systolic time intervals, radionuclide ventriculography) and exercise tolerance (treadmill exercise testing) were determined. There was no change in mean resting heart rate with the combination therapy, although one patient developed sinus bradycardia at a rate of 44 and had to have his propranolol dose reduced. Electrocardiographic analysis showed significant prolongation of the QTc intervals on lidoflazine-propranolol therapy compared to propranolol alone, with 3 patients having QTc interval prolongation to above .53 seconds, but there was no evidence of increased arrhythmogenesis with the combination therapy compared to propranolol alone. Left ventricular end-diastolic volume index tended to rise with combination therapy. However, lidoflazine-propranolol therapy did not produce any significant effects on resting ejection fraction determined by M-mode echocardiography or by radionuclide ventriculography. Radionuclide ventriculography determined peak exercise ejection fractions were also not significantly changed with combination therapy compared to propranolol alone. There were only small, insignificant improvements in exercise tolerance with the lidoflazine-propranolol combination treatment compared to propranolol alone. It is concluded that lidoflazine-propranolol combination therapy is generally safe but has the potential of causing serious adverse effects in certain patients, i.e. those with sick sinus disease, prolonged QTc intervals, and severe baseline left ventricular dysfunction, and that caution must be exercised in its use. Furthermore, it would appear that combination therapy provides only slight, if any, improvements in exercise tolerance in patients with chronic stable angina having a therapeutic response to oral propranolol.

Adult↗

PubMed1990

Differential inhibition of nucleoside transport systems in mammalian cells by a new series of compounds related to lidoflazine and mioflazine.

The sensitivity of facilitated-diffusion and Na(+)-dependent nucleoside transporters to inhibition by a series of novel compounds related to lidoflazine and mioflazine was investigated. Uridine transport by rabbit erythrocytes, which proceeds solely by the nitrobenzylthioinosine (NBMPR)-sensitive facilitated-diffusion system, was inhibited with apparent Ki values of less than 10 nM by lidoflazine, mioflazine, soluflazine and R73-335. These compounds also blocked site-specific [3H]NBMPR binding to rabbit erthrocyte membranes in a competitive fashion. The NBMPR-sensitive system in rat erythrocytes was also inhibited by lidoflazine, mioflazine, soluflazine and R73-335 but was two to three orders of magnitude less sensitive to inhibition than the system in rabbit erythrocytes (apparent Ki 7.3, 2.4, 5.7 and 0.1 microM, respectively). Lidoflazine, mioflazine and R73-335 exhibited a similar potency for the NBMPR-sensitive and -insensitive nucleoside transporters in rat erythrocytes. In contrast, soluflazine was 20- to 100-fold more potent as an inhibitor of the NBMPR-insensitive nucleoside transport component in rat erythrocytes (IC50 of 0.08-0.2 microM) compared to the NBMPR-sensitive nucleoside carrier in these cells (IC50 approximately 10 microM). None of the test compounds were potent inhibits of Na(+)-dependent uridine transport in bovine renal brush-border membrane vesicles. These results indicate that lidoflazine, mioflazine, soluflazine and R73-335 are selective inhibitors of nucleoside transport in animal cells and that the potency of these compounds as nucleoside transport inhibitors is species dependent.

Affinity Labels↗

PubMed1979

Effect of lidoflazine on membrane currents and contraction in voltage-clamped frog atrial fibers.

The effect of lidoflazine on action potential, membrane currents and contraction of frog atrial fibers was tested using the double sucrose voltage clamp technique. Lidoflazine was found to decrease the sodium conductivity of the heart cell membrane, probably by blocking the sodium channels. The availability of the sodium system at resting potential was slightly enlarged by lidoflazine and the recovery from inactivation was prolonged in most of the preparations tested. A small decrease of the slow inward current and a reduction of phasic and tonic tension was observed. The outward current at higher depolarizations was increased by lidoflazine resulting in a shortened action potential duration. The data suggest that lidoflazine's antifibrillatory properties are less pronounced than those of classical antiarrhythmic agents; but the slight antifibrillatory and negative inotropic effect might be helpful in the treatment of angina pectoris.

Animals↗