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Results for “Aprindine”

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At least 19 recordsLinked to original sources

PubMed1991

Combination therapy with aprindine and verapamil for paroxysmal supraventricular tachycardia as assessed by transesophageal atrial pacing.

UNLABELLED: To assess the efficacy of combination therapy of aprindine (40 mg/day) and verapamil (160 mg/day), transesophageal programmed atrial stimulation was performed on 21 patients with paroxysmal supraventricular tachycardia (including 12 patients with atrioventricular nodal reentrant tachycardia and nine patients with atrioventricular reentrant tachycardia) under four conditions: a) control, b) aprindine alone, c) verapamil alone, and d) aprindine + verapamil. RESULTS: a) Aprindine, verapamil, and aprindine + verapamil prevented paroxysmal supraventricular tachycardia induction in 2/21, 3/21, and 9/21 patients, respectively; b) aprindine + verapamil prolonged the cycle length of paroxysmal supraventricular tachycardia more than aprindine or verapamil alone; c) aprindine, verapamil, and aprindine + verapamil decreased the AV blocking rate by 15, 23, and 35 beats/min, respectively, in comparison with the control state; d) aprindine, verapamil, and aprindine + verapamil prolonged the effective refractory period of atrioventricular conduction system by 20, 34, and 76 msec, respectively, compared with the control state. In conclusion, aprindine + verapamil appear to be more effective than aprindine or verapamil alone in preventing paroxysmal supraventricular tachycardia with nodal reentry, but there was less benefit in those without nodal reentry (Wolff-Parkinson-White group).

Administration, Oral↗

PubMed1991

Aprindine blocks the sodium current in guinea-pig ventricular myocytes.

Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 mumol/l) on the Na+ current using whole cell voltage clamp (tip resistance = 0.5 M omega, [Na]i ando = 10 mmol/l at 18 degrees C). Aprindine revealed tonic block (Kdrest = 37.7 mumol/l, Kdi = 0.74 mumol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 +/- 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 mumol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% +/- 3% at 1.5 ms, 82% +/- 6% at 20 ms, 93% +/- 7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na+ current by 3 mmol/l tosylchloramide sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = -100 mV and 5.0 s at holding potential = -140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 mumol/l aprindine showed smaller use-dependent block (14% +/- 7% at 2 Hz; n = 4) comparing with either at pH 7.4 (68% +/- 13%; n = 4) or at pH 8.0 (90% +/- 12%; n = 4). The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na+ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule.

Action Potentials↗

PubMed1977

Treatment of recurrent ventricular tachycardia and fibrillation with aprindine.

Twenty-three patients with recurrent ventricular tachycardia or ventricular fibrillation, or both, were treated with aprindine, a new antiarrhythmic agent. It was found that: (1) no patient had a recurrence of ventricular fibrillation after aprindine therapy was begun, except as a terminal event subsequent to the development of acute myocardial infarction and cardiogenic shock or refractory congestive heart failure; (2) 6 patients experienced ventricular tachycardia after the loading dose, but with continued aprindine therapy the ventricular tachycardia was suppressed in 3 of these 6 patients, and a fourth patient was asymptomatic during brief paroxysms of ventricular tachycardia; (3) in 2 patients, aprindine was ineffective and was discontinued; (4) electrical cardioversion was not required in any patient receiving aprindine; (5) premature ventricular extrasystoles were decreased in 18 of the 23 patients treated with aprindine; (6) aprindine was discontinued in 1 patient because of intolerable side effects, although ventricular arrhythmias were suppressed in this patient; and (7) 5 patients died from acute myocardial infarction or severe heart failure while receiving aprindine.

Administration, Oral↗

PubMed1975

Antiarrhythmic and antifibrillatory properties of aprindine.

The effectiveness of aprindine, N-[3-(diethyl amino)propyl]-N-phenyl-2-indanamine, was examined against experimentally induced arrhythmias. Ouabain-induced ventricular tachycardia was reversed in six of six dogs by aprindine, 5 mg/kg i.v. The threshold for extrasytoles induced by a 250-msec train of 60 Hz 2-msec pulses starting 75 msec after the pacing pulse was elevated from a control value of 0.18 +/- mA to a peak of 0.29 +/- 0.03 mA 5 minutes after aprindine, 5 mg/kg (P less than .005). The similarly determined ventricular fibrillation threshold was increased from a control value of 2.45 +/- 0.78 mA to a maximum of 5.68 +/- 1.47 mA 30 minutes after aprindine, 5 mg/kg i.v. (P less than .025). Aprindine failed to protect against fibrillation associated with one-stage occlusion and release of the left anterior descending coronary artery. Conscious dogs 24 hours after two-stage ligation of the left anterior descending coronary artery showed ectopic beats averaging 107 +/- 5 beats/min. Aprindine, 5 mg/kg i.v., caused an initial reduction of the ectopic rate to 1 +/- 1 beats/min (P less than .001) returning to 57 +/- 19 beats/min (P less than .05) 30 minutes postdrug. An additional 5 mg/kg dose reduced the ectopic rate to 1 +/- 1 beats/min (P less than .001) returning to 15 +/- 8 beats/min (P less than .005) 60 minutes after drug. Evaluation of these animals at 48 hours showed a similar pattern, although one animal fibrillated after 5 mg/kg of aprindine. Aprindine is an effective antiarrhythmic agent in some experimental cardiac arrhythmias, but the appearance of central nervous system toxicity at therapeutic drug concentrations in conscious animals indicates that it may have a narrow margin of safety.

Animals↗

PubMed1976

GLC determination of aprindine: quantitation and stability measurement.

A GLC method of analysis of a new antiarrhythmic agent, aprindine, is described. The raw material of the new drug substance, supplied as the hydrochloride salt, is dissolved in deionized water, and the base is liberated by a 10% aqueous solution of sodium carbonate. aprindine is extracted with chloroform and mixed with the internal standard, 5alpha-cholestane. GLC is perfomed on a glass column packed with 3.8% W-98 on Chromosorb W-HP. Quantitation is achieved by computer calculation of the peak area ratios. GLC-mass spectral analysis indicates that the observed peak is that of aprindine, with a molecular ion at m/e 322. The retention times of aprindine and the internal standard are 2.0 and 5.8 min, respectively. All synthetic precursors show a shorter retention time than aprindine. This GLC method is applied to the quantitative determination of aprindine as raw material and in capsule and ampul formulations. The method is also used to measure the stability of aprindine to acid, base, dry, heat, refluxing, and UV light and to pH variations.

Aprindine↗

PubMed1978

Suppression of the repetitive ventricular response: an index of long-term antiarrhythmic effectiveness of aprindine for ventricular tachycardia in man.

The repetitive ventricular response, defined as the production of two or more ventricular premature complexes in response to a single ventricular pacing stimulus, is common in patients with serious ventricular arrhythmias. Twenty-seven patients with refractory ventricular tachycardia were studied to determine whether acute suppression of the repetitive ventricular response by aprindine predicts long-term effectiveness of this agent. Twenty-three of the 27 patients had the repetitive ventricular response before intravenous administration of aprindine, whereas only 6 had the response after aprindine. All patients were maintained on a regimen of oral aprindine and evaluated repeatedly for a mean of 12 months. Twenty of the 21 patients who had no repetitive ventricular response after intravenous aprindine manifested clinical improvement compared with only 1 of the 6 in whom the repetitive response was present after aprindine (P less than 0.0005). Aprindine is a useful agent in refractory ventricular tachycardia, and the absence of the repetitive ventricular response after its intravenous administration predicts long-term clinical responsiveness to the oral form.

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↗

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↗

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↗

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↗

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↗

PubMed1975

Effects of aprindine HCL on cardiac tissues.

The effects of aprindine HCL on cardiac tissues were studied in anesthetized, open-chest dogs pretreated with atropine (0.8 mg/kg) and propranolol (1.0 mg/kg). Aprindine (10(-5)-10(-3) g/ml), injected into the sinus node artery, decreased the spontaneous sinus rate; when injected into the atrioventricular nodal artery, aprindine (10(-4) g/ml) prolonged the conduction time and functional refractory period of the atrioventricular node. Intravenous administration of aprindine (1.4, 2.8 and 4.2 mg/kg cumulative dose) prolonged atrial and ventricular conduction time and prolonged the effective refractory period of both tissues. The results from this study indicate that aprindine has a negative dromotropic effect on all cardiac tissue.

Animals↗

PubMedDate not supplied

Experimental study on the electrophysiological effects of the combination of the antiarrhythmic drugs aprindine and verapamil.

The acute electrophysiological effects of the antiarrhythmic drugs aprindine and verapamil, injected intravenously either alone or in combination, were studied in 14 dogs during invasive electrophysiology. The AH and HV intervals during sinus rhythm were significantly prolonged, especially in the aprindine and the aprindine plus verapamil groups. The cycle lengths of the antegrade and retrograde atrio-ventricular block were most prolonged in the combination group. The effective refractory period and the functional refractory period of the atrial tissue, as well as the functional refractory period of the atrio-ventricular node, the effective refractory period of ventricular tissue and the ventriculo-atrial conduction system were most prolonged when the combination of the agents was given. The effective refractory period of the atrio-ventricular node was prolonged in the groups receiving verapamil and verapamil plus aprindine. There was no significant difference in the serum concentration of each agent given alone or in combination. These results suggest that the efficacy of the combination of verapamil and aprindine may be due to additive or synergistic effects of these antiarrhythmic agents.

Animals↗

PubMed1975

Absorption, half-life, and toxicity of oral aprindine in patients with acute myocardial infarction.

Plasma concentrations of aprindine were used to assess its absorption, toxicity and disappearance rate after oral administration to patients within 24 hours of admission to a coronary care unit. Despite high oral doses, absorption was so slow that in half the patients effective plasma levels (exceeding 0.70 mug/ml) were not found during the first 12 hours of treatment. Therefore the oral route should not be used to treat cases of acute myocardial infarction with severe ventricular dysrhythmias. Clinical tolerance was good; there was one episode of delirium tremens in a chronic alcoholic (aprindine plasma concentration: 3 mug/ml); no case of tremor or cerebellar syndrome was observed. Disappearance of aprindine from plasma was slow, by far exceeding the half-lives found in healthy volunteers, and ranging from 20 to over 100 h. The variability of biological half-life in individual patients makes plasma level determiniations necessary whenever aprindine is to be administered for a long period.

Administration, Oral↗

PubMed1991

Effects of aprindine on monophasic action potentials.

Using a catheter electrode developed by the authors for recording monophasic action potentials (MAPs), the atrial and ventricular MAPs of seven mongrel dogs were simultaneously recorded. The results were used to evaluate the effect of the new antiarrhythmic drug aprindine on MAPs. An electrophysiologic study was also carried out to evaluate the effect of aprindine on the conduction system. Aprindine caused a significant increase in both the AH interval (at a basic cycle length of 400 ms) and the HV interval (at basic cycle lengths of 400 and 500 ms). The effective refractory period increased in both the right atrium and the right ventricle. Although an increase in MAP duration at repolarizations to 90% MAP (MAPD90) was not observed in the right atrium, a significant increase was noted in MAPD90 in the right ventricle. There were no significant changes in the ratio between the effective refractory period and MAPD90 of the right ventricle before and after administration of aprindine. This result suggests that increases in MAPD90 contribute to an increase in the effective refractory period of the right ventricle.

Action Potentials↗

PubMed1977

Development of a radioimmunoassay for aprindine.

We have developed a radioimmunoassay for aprindine, a new antiarrhythmic drug used in the treatment of ventricular disorders. The antibodies were produced by immunization of New-zealand rabbits with aprindine coupled to human serum albumin. Their biochemical characteristics have been determined. Tritiated aprindine was used as radioactive competitor. The cross-reactivity with several metabolites of aprindine was studied too. Finally, the results obtained by RIA in plasma and tissues of dogs were compared to those obtained by gas-chromatography.

Animals↗

PubMed1992

Aprindine-induced hepatic granulomata.

Aprindine is a very effective antiarrhythmic agent with a narrow therapeutic ratio. We report a patient who suffered from granulomatous hepatitis probably due to the administration of aprindine. Evidence of hepatitis appeared within 6 weeks of initiating aprindine therapy and resolved rapidly when the drug was withdrawn. Six months later, fibrosis but no granulomata were found in the expanded portal tracts. Our observations suggest that granulomatous hepatitis can occur during aprindine therapy.

Aprindine↗

PubMed1977

Cardiovascular and antiarrhythmic effects of aprindine (AC1802) during partial occlusion of a coronary artery in the pig.

The effect of intravenously administered aprindine (AC1802) as a prophylactic agent against ventricular arrhythmias was studied in pigs. During the first 30 min of ischaemia 5 of the 22 untreated animals died because of ventricular fibrillation against 1 of the 23 animals pretreated with aprindine (P=0.09). Ventricular tachycardias were observed in 10 untreated animals and in none of the aprindine group (P=0.0002). The incidence of other arrhythmias was significantly less in the aprindine group compared with the untreated group (P less than 0.02).

Animals↗