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At least 37 records · Page 2Linked to original sources
PubMed1995

Effects of aprindine on electrophysiological properties of the atrial muscle in man.

The effects of aprindine on atrial vulnerability were studied in 11 patients; 9 with paroxysmal atrial fibrillation (PAF), and 2 with Wolff-Parkinson-White syndrome, aged 19 to 69 (55.9 +/- 16.5; mean +/- SD). Before and 10 min after the intravenous injection of aprindine (1.5 mg/kg), programmed extrastimulation was performed from the right atrial appendage. Atrial vulnerability was assessed by evaluating the repetitive atrial firing zone (RAFZ), conduction delay zone (CDZ), maximum conduction delay (Max. CD) and fragmented atrial activity zone (FAAZ). After the injection, the duration of the P wave and QTc interval was significantly prolonged without any change in blood pressure or heart rate. RAF was observed in 8 patients under control conditions. However, after the injection of aprindine, the RAFZ completely disappeared in 2 patients, was narrowed in 4, and became wider in 1. AF was induced in the remaining patient. The zone significantly reduced (p < 0.01) without any change in CDZ or Max. CD. While FAA was observed in 5 patients under control conditions, it completely disappeared in 2 patients, was narrowed in 1, and did not change in the remaining 7 after the injection of aprindine. In patients whose RAFZ narrowed after administration of aprindine, the wavelength, as determined from the atrial effective refractory period and conduction velocity, was augmented. These results indicate that aprindine suppresses atrial vulnerability with an augmentation of the wavelength. However aprindine exaggerated atrial vulnerability in some patients, such that atrial fibrillation was induced.

Action Potentials↗
PubMed1987

Competitive inhibition of cardiac sodium channels by aprindine and lidocaine studied using a maximum upstroke velocity of action potential in guinea pig ventricular muscles.

An interaction between aprindine and lidocaine on cardiac fast sodium channels was investigated in isolated guinea pig ventricular muscles. A conditioning clamp pulse was applied from -90 to 0 mV through the single sucrose gap voltage clamp, and the maximum upstroke velocity (Vmax) of action potential elicited after the clamp pulse was measured as an index of sodium channel availability. In the presence of aprindine (2 and 5 microM) or lidocaine (20 and 40 microM), Vmax of test action potential 100 msec after the clamp pulse was decreased progressively as the clamp pulse duration was prolonged. The time constant of this inactivated channel block by aprindine was much slower than by lidocaine. Vmax after a 1000 msec clamp pulse recovered exponentially with a time constant of 4.75 to 4.81 sec for aprindine and 254 to 260 msec for lidocaine. In the presence of both aprindine and lidocaine, Vmax recovered in dual exponential function, where the short and the long time constant corresponded to the values for single treatment with each drug. In preparations treated with aprindine alone the use-dependent decrease of Vmax was observed during stimulation trains at rates higher than 0.1 Hz. This use-dependent block was attenuated significantly after additional application of lidocaine resulted in a net increase in Vmax at 0.5 to 1.0 Hz. These findings suggest that aprindine and lidocaine may block the sodium channels by binding to a common receptor site with different kinetics, leading to a competitive displacement with each other at their high concentrations.

Action Potentials↗
PubMed1981

Effect of aprindine on transmembrane currents and contractile force in frog atria.

The effects of aprindine on transmembrane currents in frog (Rana Ridibunda) atrial trabeculae were studied using a voltage clamp technique. Aprindine (1 x 10(-6) g/ml) reduced maximum inward sodium current by 38.6 +/- 7.2% (mean +/- S.E.M., n = 6), but had no effect on the slow inward current or outward current. A higher dose of aprindine (2.8 +/- 10(-5) g/ml) suppressed both the fast inward current and the slow inward current. Outward current was decreased at membrane potentials between -80 and -45 mV and increased at membrane potentials positive to -20 mV. In addition, aprindine was tested on frog (R. Ridibunda) atrial strips in which the transmembrane action potential and contractile force were recorded. The low dose of aprindine (1 x 10(-6) g/ml) depressed action potential amplitude and dV/dt and slightly increased action potential duration, but had no effect on contractile force. The higher dose (2.8 x 10(-5) g/ml) significantly reduced developed tension and dP/dt, decreased action potential amplitude and dV/dt and increased action potential duration. Aprindine (2.8 x 10(-5) g/ml) also depressed slow channel dependent membrane oscillations induced in atrial trabeculae by injection of current pulses. These data indicate that aprindine possesses fast and slow channel blocking properties, the latter being more apparent at high concentrations of the drug, and affects outward current differentially, depending on the membrane potential.

Animals↗
PubMed1997

Chronic administration of aprindine during maintenance hemodialysis.

Aprindine was administered for 12 months to 8 hemodialysis patients suffering from arrhythmias. The serum aprindine concentration ranged from 0.3 to 0.6 microgram/ml, and did not increase with time during the 1-year treatment period. The PQ interval was temporarily prolonged in the first and second months, but the QRS and QT intervals were not changed by chronic aprindine treatment. The changes of the PQ interval in the second month of treatment were directly correlated with the serum aprindine concentration. No alterations of the ECG findings were observed when aprindine was discontinued. The cardiothoracic ratio (chest radiography) and laboratory findings were also not influenced by either aprindine treatment or its withdrawal. In conclusion, aprindine may be safely administered for at least 1 year to arrhythmia patients on maintenance hemodialysis.

Administration, Oral↗
PubMed1991

Effects of aprindine on conduction velocity and Vmax in guinea-pig papillary muscles.

One of the effects of antiarrhythmic drugs is the reduction of conduction velocity. Cable theory predicts that there is a nonlinear relationship between conduction velocity and upstroke velocity (Vmax) of action potential. By using conventional microelectrode techniques, aprindine-induced reduction of Vmax of action potential and conduction velocity in guinea-pig papillary muscles were measured. Aprindine-produced, use-dependent, and concentration-dependent changes in conduction velocity and the decline of square of conduction velocity was well fit by a single exponential. Time constants for square of conduction velocity were comparable to simultaneously measured time constants for effects of Vmax. At a concentration of 1 to 10 microM aprindine, onset changes between Vmax and conduction velocity had a log-linear relationship in a predicted fashion. Whereas, in the recovery process from aprindine-induced depression, slow recovery time course of conduction velocity was observed. In conclusion, in the presence of aprindine, only onset block of conduction velocity can be analyzed quantitatively in the relationship to observation on Vmax in vitro. These results suggested that in the presence of aprindine, the recovery of internal conductance may be slower than that of Vmax.

Action Potentials↗
PubMed1982

Binding of aprindine and moxaprindine to human serum, alpha 1-acid glycoprotein and serum of healthy and diseased humans.

A comparison was made between the binding of the anti-arrhythmic agents aprindine and moxaprindine to human serum, to human serum albumin (HSA), to alpha 1-acid glycoprotein (alpha 1-AGP) and to a mixture of HSA and alpha 1-AGP. In serum from healthy volunteers (n = 4) the binding of aprindine-HCl 5 micrograms/ml (13.8 microM) was 93.8% (SD +/- 1.0), and that of moxaprindine-HCl 5 micrograms/ml (12.8 microM) was 94.15 (SD +/- 1.1). Their binding to the mixture of alpha 1-AGP and albumin approximated their binding to serum. For alpha 1-AGP, the binding was similar for both compounds, whereas for HSA the binding of aprindine was more pronounced than that of moxaprindine: for both products the affinity coefficient for binding to alpha 1-AGP was about 100 times greater than that for binding to albumin. In serum from rheumatoid patients and from patients with renal failure a small but significant increase in binding of aprindine and moxaprindine was observed, approximately 1%. Increased and decreased binding was seen in serum from cirrhotic patients; for example, for aprindine the range in cirrhosis was 96.7%-79.8%, and the range in controls was 95.0%-92.4%. Free drug fraction and alpha 1-AGP concentration were inversely correlated. The results show that alpha 1-AGP plays an important role in the binding of aprindine and moxaprindine, and that alteration in the binding of the two compounds in disease states to a large extent can be explained by changes in serum alpha 1-AGP concentration.

Aprindine↗
PubMed2005

Effect of antiarrhythmic agents on heart rate variability indices after myocardial infarction: comparative experimental study of aprindine and procainamide.

The cardiac arrhythmic suppression trial (CAST) reported that antiarrhythmic treatments in post-myocardial infarction (MI) patients resulted in poor outcome and decreased in heart rate variability indices (HRV). The goal of the present study was to determine whether aprindine and procainamide, antiarrhythmic agents that increase HRV, result in beneficial effects in post-MI rabbits. Four weeks before experiment, MI was induced in four rabbits by ligating the major branch of left coronary artery. A total of eight rabbits (four post-MI and four normal rabbits) were randomly assigned to treatment with either intravenous aprindine (1 mg/kg) or intravenous procainamide (15 mg/kg). Frequency domain HRV (low frequency spectra, LF, 0.04-0.15 Hz; high frequency spectra, HF, 0.15-0.40 Hz) were assessed by MemCalc software. Aprindine significantly increased HF and LF in both MI and normal rabbits, whereas procainamide tended to decrease HF and LF in MI and normal rabbits (in total rabbits; aprindine, LF, from 6.3 +/- 7.9 to 16.5 +/- 15.0 ms(2)/Hz, P < 0.05; HF, from 8.0 +/- 11.7 to 17.5 +/- 15.0 ms(2)/Hz, P < 0.05; procainamide, LF, from 4.9 +/- 7.4 to 4.8 +/- 8.5 ms(2)/Hz, NS; HF, from 11.1 +/- 23.0 to 5.1 +/- 10.6 ms(2)/Hz, NS). Under pharmacological denervation with propranolol (0.1 mg/kg) and atropine (0.04 mg/kg), aprindine increased LF and HF (LF, from 0.2 +/- 0.2 to 0.8 +/- 0.7 ms(2)/Hz, P < 0.05; HF, from 0.1 +/- 0.0 to 0.2 +/- 0.0 ms(2)/Hz, P < 0.05). These data suggest that aprindine can increase HRV in post-MI rabbits. Further experiments in human subjects would be of benefit.

Adrenergic beta-Antagonists↗
PubMed1987

Frequency- and voltage-dependent effects of aprindine on the upstroke velocity of action potential in guinea pig ventricular muscles.

The effects of aprindine on transmembrane action potentials were examined in isolated papillary muscles of guinea pig. Aprindine (10(-6)-10(-5) M) caused a dose-dependent decrease in the Vmax of the action potential without affecting the resting potential. In the presence of aprindine, trains of stimuli at rates greater than 0.1 Hz led to an exponential decline in Vmax. This use-dependent block was enhanced at the higher stimulation frequency. The time constant for the recovery of Vmax from the use-dependent block (offset) was 6.2-7.8 s. In depolarized papillary muscles with high [K+]o, the inhibitory action of aprindine on Vmax after a long quiescent period (tonic block) was augmented markedly, but the rates of onset and offset of the use-dependent block were similar to those in normally polarized preparations. The curves relating membrane potential and Vmax were shifted by 7.3 mV with aprindine at 3 X 10(-6) M in the direction of more negative potentials. These findings suggest that aprindine has quinidinelike use-dependent inhibitory action on the fast sodium channels of cardiac muscles. This use-dependency and its greater inhibition of Vmax in depolarized muscles through the augmentation of tonic block may play a major role for the drug action to prevent ventricular arrhythmias.

Action Potentials↗
PubMed1982

Effect of 2 anti-arrhythmic drugs aprindine and moxaprindine on the replication capacity of murine and human haemopoietic cells.

Aprindine, a potent anti-arrhythmic agent, occasionally seems responsible for agranulocytosis. In order to study its potential haematological toxicity, 3 different in vitro tests were used: (a) the capacity of human and mice bone marrow to incorporate tritiated thymidine (3HTdR), (b) the capacity of stimulated human blood lymphocytes to incorporate 3HTdR and (c) the capacity of human granulocyte-macrophage stem cells to form colonies in agar. For all these tests aprindine was found to be toxic at concentrations close to the clinical therapeutic serum concentration. Moxaprindine, chemically very close to aprindine exhibits also an anti-arrhythmic activity. It was examined in the same tests in parallel with the study af aprindine. Moxaprindine also exhibited haematological toxicity in the tests but at a significantly higher concentration, approximately twice that of aprindine. Assuming that these in vitro tests are relevant to the in vivo haematological toxicity, moxaprindine could be considered a clinically safer anti-arrhythmic agent than aprindine.

Animals↗
PubMed1990

[Effects of intravenous aprindine on hemodynamics in patients with cardiac dysfunction and its pharmacodynamics in patients with premature ventricular contractions].

The effects of aprindine, 100 mg iv, on hemodynamics, and the relationship between its inhibitory effect on PVC and its levels in the blood were determined in patients with diminished cardiac function. PVC was inhibited in 7 of 13 patients (54%), compared with a 50% inhibition rate in controls. The levels of aprindine in the blood after intravenous administration, rapidly decreased from 1.78 +/- 1.09 micrograms/ml immediately after administration, to 0.80 +/- 0.25 micrograms/ml after 15 min, to 0.65 +/- 0.23 micrograms/ml after 30 min and to 0.56 +/- 0.19 micrograms/ml after 1 hour. The duration of blood levels of 0.55 +/- 0.35 micrograms/ml, which are the levels presumed to be effective, was one hour after administration. The mean elimination half-life of aprindine was 18.9 +/- 8.4 hours. Aprindine produced relatively little effect on hemodynamics in patients with moderate to severe heart failure, but when its effects in individual cases were studied, it was found that aprindine elicited such changes as reduction in cardiac index, stroke volume index and stroke work index, and elevation in pulmonary arterial diastolic pressure. These findings suggest that care should be exercised in aprindine therapy in patients with diminished cardiac function. At least there should be monitoring of blood pressure and heart rate at appropriate times after intravenous administration.

Adult↗
PubMed1989

[Clinical effects and plasma concentration levels of aprindine hydrochloride in patients with tachyarrhythmias].

Aprindine hydrochloride (aprindine) was administered orally in 17 Japanese patients with supraventricular or ventricular tachyarrhythmias, and the clinical effects and plasma concentration levels were evaluated. The antiarrhythmic effects were defined using Holter ECG recordings. Aprindine was administered orally with a daily dose of 40 mg for 2 weeks in all cases, and aprindine, 60 mg daily, was administered for the next 2 weeks in patients who did not show sufficient antiarrhythmic effects with 40 mg of the drug. Aprindine was effective in 9 of 17 patients, and the mean plasma concentration level reached 0.6 micrograms/ml 2 weeks after the administration was started. Effective results were seen in 2 of the 4 patients receiving a daily dose of 60 mg, and the mean plasma concentration level reached 1.0 microgram/ml 2 weeks after the administration was started. Transient mild elevations of liver transaminases were observed in one patient and mild transient anemia was observed in another. These abnormal data disappeared although the drug administration was continued. In conclusion, the administration of a relatively small dose of aprindine and, consequently, low plasma concentration levels, are effective for cardiac tachyarrhythmias in Japanese patients.

Administration, Oral↗
PubMed1978

Effects of aprindine HCl on slow channel action potentials and transient depolarizations in canine Purkinje fibers.

The electrophysiologic effects of aprindine hydrochloride were studied on normal Purkinje fibers, on Purkinje fibers superfused with Tyrode's solution containing 22 mM KCl and isoproterenol (1 X 10(-5) M) and on transient depolarizations induced by exposure to acetylstrophanthidin (1.7--2 X 10(-7) M). Aprindine (3 X 10(-6) M) significantly reduces the action potential amplitude and dV/dtmax and shortens the action potential duration but does not alter the resting membrane potential. Transient depolarizations were suppressed by aprindine at a dose of 2 X 10(-6) M. Isoproterenol (1 X 10(-5) M) failed to restore the transient depolarizations after suppression with aprindine. Slow responses induced in K-depolarized, isoproterenol-treated fibers were unchanged by aprindine (3 X 10(-6)-1 X 10(-5) M) in the presence as well as in the absence of acetylstrophanthidin. These experiments suggest that aprindine does not have slow channel blocking properties and that an inward current through the slow channel cannot be considered as the sole basis of the digitalis-induced transient depolarization.

Action Potentials↗
PubMed1983

[Detection of aprindine and its metabolites in plasma and urine].

In 36 patients with cardiac arrhythmias (predominantly ventricular premature beats), who were on oral aprindine long-term therapy with 50 to 400 mg daily, plasma levels were measured by gas chromatography after 3.5 hours of the last administration. There was a general dependency of plasma levels on the given dose, however, with considerable overlapping in individual values. In 24 patients the arrhythmias ceased, in six patients there was a clear, in two a moderate improvement. There was no clear therapeutic effect in four patients who were treated with a daily dose of 50 and 100 mg, respectively. Among the 36 patients, three who had plasma levels exceeding 2 micrograms/ml developed tremor and dizziness. After dose-reduction these side effects disappeared. The present results suggest that therapeutic plasma levels of aprindine are in the range of 1.0 to 1.75 micrograms/ml. A plasma level of 2 micrograms/ml should not be exceeded because of the possibility of side-effects. In six healthy males time-concentration curves of aprindine and its metabolites in plasma and urine were measured by gas chromatography. From the results a two-compartment model may be applied, the half-life of elimination was calculated to be 37 hours (plasma) and 31 hours (urine). With respect to the metabolites, in plasma only des-ethyl-aprindine (DEAP), in urine DEAP, hydroxy-, des-phenyl- and des-indanyl-aprindine could be found. Unlike aprindine, the DEAP-concentration curve in plasma showed a very slight decrease until the end of the 96-hour period of determination.

Aprindine↗
PubMed1986

Effect of sotalol, aprindine and their combination on maximum upstroke velocity of action potential in guinea-pig papillary muscle.

Microelectrode experiments were performed on papillary muscle of 11 guinea-pigs at driven heart rates of 60 and 120 b.p.m. to study the effect of sotalol 10(-4) M, aprindine 10(-6) M and the combination of both on Vmax, action potential duration and effective refractory period. Only sotalol exerted tonic Vmax block. Aprindine, sotalol and their combination produced an increase in phasic, combined tonic and phasic, and in steady state Vmax block: the effect of the combination on these parameters being larger than the effect of the single agents alone. Action potential duration was lengthened by both drugs and their combination. A statistically significant increase in effective refractory period was observed for sotalol and the combination sotalol-aprindine but not for aprindine. It can be concluded that simultaneous application of sotalol and aprindine enhances phasic, combined tonic and phasic, and steady state Vmax block with an unchanged effect of sotalol on repolarization. The effect of combinations can be explained on the basis of competition for the same receptor in the Na+ channel.

Action Potentials↗
PubMed1988

Comparative study of the block of Vmax by aprindine and quinidine in the guinea-pig heart muscle.

The depression of Vmax of the action potential in guinea-pig ventricular muscle by aprindine and quanidine was compared. Aprindine caused a more pronounced rate-dependent block (Kd = 10(-6) M at 3.3 Hz) than did quinidine (Kd = 1.6 X 10(-5) M at 3.3 Hz). Aprindine shifted the relationship between Vmax and resting potential to a more negative potential (mean 9.2 mV: 10 microM) than did quinidine (mean 5.7 mV: 10 microM). In addition, aprindine caused a more pronounced resting block (Kd = 1.3 X 10(-5) M) than quinidine (Kd = 8.6 X 10(-5) M). It is concluded that aprindine has a higher affinity for activated and/or inactivated and resting state channels than quinidine, making channels unavailable for conduction upon activation.

Action Potentials↗
PubMed1991

Agranulocytosis associated with aprindine and other antiarrhythmic drugs: an epidemiological approach.

The risk of agranulocytosis associated with anti-arrhythmic drugs has been assessed by studying previous drug exposure of all cases collected through a multicentre surveillance network in a defined geographical area during the period 1980-1988. One hundred and eighty-one patients with agranulocytosis (less than 500 granulocytes mm-3 at least in two different blood counts) were interviewed with a structured questionnaire. Eight cases attributable to anti-arrhythmic drugs were identified, all of them related to aprindine. Data on the consumption of several anti-arrhythmic drugs were identified, all of them related to aprindine. Data on the consumption of several anti-arrhythmic drugs (amiodarone, aprindine, quinidine, propafenone) were obtained in order to estimate the risk of agranulocytosis related with the previous use of these drugs. A relevant risk was identified only for aprindine, of the order of two cases per 1000 patient-years. Our data suggest that the risk of agranulocytosis associated with aprindine is lower than previously found.

Aged↗
PubMed1980

The binding of aprindine to serum proteins with statistical considerations concerning the analysis of binding data.

The binding of the potent, basic antiarrhythmic agent aprindine to serum proteins was studied in solutions of human serum albumin (HSA, lyophilized, 98% pure, KABI) and in human sera. The percentual binding in serum (90.9-96.7%) was considerably higher than in HSA solutions. The binding in serum decreased from 95-97% to 91-93% as the aprindine concentration was raised from 4 to 15 micrograms/ml. The serum binding differed significantly in sera from three normal individuals. By plotting (Formula: see text), as a function of bound drug and performing statistical analysis of the curves a striking difference between the number of primary binding sites in serum and in HSA solution was found (N1 for the HSA solution was 0.0016 and for one serum it was 0.020 "per albumin molecule".) The association constants for the primary binding sites (K1) were 4.3 X 10(6)M-1 for serum and 2.1 X 10(6)M-1 for the HSA solution. Furthermore, the analysis indicated that considerably less than one secondary binding site was present for each albumin molecule in the HSA solution. Therefore, no binding of aprindine to albumin molecules has been demonstrated and it is concluded that the entire binding of aprindine in serum as well as in 98% HSA solutions may be due to the presence of acid protein molecules. In particular, low percentual binding in HSA solutions in spite of the high association constant can be explained by a very low concentration of the binding proteins. The addition of propranolol or phenprocoumon did not cause any displacement of aprindine. In the appendix statistical problems in the analysis of the binding curves are elucidated. The experimental variance and the statistical acceptability of the binding model are discussed.

Analysis of Variance↗
PubMed1977

Suppression of refractory arrhythmias by aprindine in patients with the Wolff-Parkinson-White syndrome.

Four patients with supraventricular tachycardia associated with the Wolff-Parkinson-White syndrome were refractory to conventional pharmacological therapy and received aprindine hydrochloride intravenously and orally. Electrophysiological studies disclosed that intravenous aprindine caused increased refractoriness and slowed conduction in the atria, atrioventricular node, ventricles, and accessory pathway. The ability to induce supraventricular tachycardia with timed atrial and ventricular premature stimuli was totally abolished in all 4 patients after intravenous aprindine. Oral aprindine therapy, twice daily thereafter, provided symptomatic relief of the supraventricular tachycardia without significant side effects. Aprindine is useful in the management of supraventricular tachycardia associated with Wolff-Parkinson-White and may offer significant advantages over currently available therapy.

Administration, Oral↗