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At least 19 recordsLinked to original sources
PubMed1981

Ventricular tachycardia: prediction of response to oral aprindine with intravenous aprindine.

Aprindine was administered both intravenously and orally to 25 patients with ventricular tachycardia refractory to conventional antiarrhythmic agents to test the hypothesis that the response to intravenous aprindine predicts the response to oral aprindine. Ten patients had incessant ventricular tachycardia and 15 had paroxysmal sustained inducible ventricular tachycardia. Eleven patients (43 percent) had conversion to sinus rhythm with intravenous aprindine (nine with incessant and two with paroxysmal sustained ventricular tachycardia). Thirteen patients (all with paroxysmal sustained ventricular tachycardia) manifested slowing of the tachycardia without conversion, whereas in one patient with incessant ventricular tachycardia, the tachycardia became less frequent and nonsustained after intravenous aprindine. All 11 patients who had conversion to sinus rhythm with intravenous aprindine remained free of ventricular tachycardia during oral treatment with aprindine (at 2 weeks) and for a follow-up period of 2 to 38 months (mean 16 +/- 13). Of the 14 patients who did not have conversion to sinus rhythm with intravenous aprindine, 12 had spontaneous or inducible ventricular tachycardia, or both, at evaluation 1 to 2 weeks after initiation of oral aprindine. In conclusion, administration of intravenous aprindine to patients with ventricular tachycardia is helpful in predicting the subsequent response to oral aprindine. In addition, the pattern of ventricular tachycardia predicted the response to aprindine; patients with incessant ventricular tachycardia tended to respond, and those with paroxysmal sustained ventricular tachycardia tended not to respond.

Administration, Oral↗
PubMed1986

Effect of sotalol, aprindine and the combination aprindine-sotalol on monophasic action potential duration.

The effects of sotalol, aprindine and the combination aprindine-sotalol in the intact dog heart were evaluated during constant atrial pacing with the use of monophasic action potential (MAP) recording. A first group of five dogs was given 1.5 mg kg-1 body weight of sotalol, followed by a second infusion of 1.5 mg kg-1 30 min later. Both doses of sotalol produced a statistically significant increase in right atrial MAP duration at 50% of repolarization (RAMAP50) and right ventricular MAP duration at 90% of repolarization (RVMAP90). To a second group of six dogs aprindine 1 mg kg-1 and aprindine 2 mg kg-1 were administered intravenously. The infusion of aprindine did not alter right atrial and right ventricular MAP duration. The addition of 1.5 mg kg-1 of sotalol to the dogs pretreated with aprindine 2 mg kg-1 resulted in a 25% increase in RAMAP50 and a 21% prolongation of RVMAP90. In summary, sotalol lengthens atrial and ventricular monophasic action potential duration and still prolongs repolarization of monophasic action potentials after previous administration of aprindine. A combination of sotalol, a beta-adrenergic blocker possessing class III efficacy, with a class I antiarrhythmic agent may be useful with respect to their electro-physiological action.

Animals↗
PubMed1987

Effects of intravenous sotalol, aprindine and the combination of sotalol and aprindine on chronic high frequency ventricular arrhythmias in man.

The comparative antiarrhythmic efficacy of three different intravenous drug regimens was evaluated in 12 symptomatic patients (mean age: 72 years) with chronic high frequency ventricular arrhythmias (mean: 834 PVCs h-1). In a cross-over study with latin square distribution the following drug regimens were administered intravenously to all patients aprindine 2 mg kg-1, sotalol 1.5 mg kg-1, aprindine 1 mg kg-1 & sotalol 0.75 mg kg-1. The mean percentage of PVC reduction was 41% (P less than 0.05) for aprindine 2 mg kg-1; 51% (P less than 0.05) for sotalol 1.5 mg kg-1 and 72% (P less than 0.01) for the combined drug therapy (aprindine 1 mg kg-1 and sotalol 0.75 mg kg-1). The mean plasma concentration was 1371 ng ml-1 after administration of aprindine 2 mg kg-1 and 1730 ng ml-1 after infusion of sotalol 1.5 mg kg-1. After combined drug therapy, mean plasma levels were 942 ng ml-1 for aprindine and 992 ng ml-1 for sotalol. The different drug regimens were well tolerated in all patients and no side-effects occurred. Combination therapy consisting of a drug that prolongs action potential duration with an antiarrhythmic agent that has a high affinity for the inactivated channels may thus achieve an antiarrhythmic efficacy comparable to single agent therapy, permitting the use of lower dosages.

Aged↗
PubMed1981

Alterations in regional myocardial distribution and arrhythmogenic effects of aprindine produced by coronary artery occlusion in the dog.

Little information exists regarding the effects of coronary artery occlusion on the distribution and actions of antiarrhythmic agents. We administered aprindine to dogs before, 5 min after, and 24 h after one-stage left anterior descending coronary artery (LAD) occlusion. Coronary artery occlusion performed after aprindine administration slowed the rate of disappearance of aprindine from the ischaemic zone compared with the normal zone, so that ischaemic zone aprindine concentrations averaged more than twice normal zone aprindine concentrations 1 h after LAD occlusion. When LAD occlusion was performed before aprindine administration, ischaemic zone aprindine concentrations were initially less than 15% of normal zone aprindine concentrations and increased with time to approach half of normal zone aprindine concentrations 70 min after LAD occlusion. Seventeen of 35 dogs (49%) receiving aprindine before LAD occlusion experienced sustained ventricular tachycardia or ventricular fibrillation, compared with 5/34 (14%) receiving aprindine immediately after LAD occlusion (P less than 0.01), 1/10 (10%) undergoing LAD occlusion without receiving aprindine (P less than 0.05) and 0/16 receiving aprindine without LAD occlusion (P less than 0.01). Aprindine administered 24 h after CO reduced premature ventricular complexes from a mean of 35 to 12 per 100 beats (P less than 0.01) occlusion importantly modifies the regional myocardial distribution of aprindine and its effects on ventricular arrhythmias after coronary artery occlusion.

Animals↗
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↗
PubMed1990

Electrophysiologic actions of aprindine in rabbit atrioventricular node.

Aprindine hydrochloride is a potent antiarrhythmic agent against various atrial and ventricular tachyarrhythmias. To elucidate its pharmacological actions in the atrioventricular node, electrophysiologic experiments were conducted by applying microelectrode and voltage clamp methods to small preparations of the rabbit atrioventricular node. At a concentration 1 mumol/l, aprindine decreased the spontaneous firing frequency, maximal rate of depolarization, action potential amplitude, and take-off potential (P less than 0.05, n = 7). The spontaneous and rate-controlled action potential durations at 50 and 100% repolarization were prolonged by aprindine. Voltage-clamp experiments using the double microelectrode method revealed that aprindine blocked the slow inward current (Isi) in a voltage-dependent manner with a dissociation constant of 10 mumol/l and Hill coefficient of 0.8. The steady-state inactivation curve for Isi was shifted toward more negative potentials by 2.5 +/- 0.9 mV (P less than 0.05, n = 5) without a significant change in the slope factor. This finding suggests that aprindine has a higher affinity for inactivated slow inward (or Ca2+) channels than for resting channels. Aprindine caused use-dependent block of Isi, a result consistent with the drug's slow dissociation from inactivated Ca2+ channels. The delayed rectifying K+ current (IK) tail obtained on repolarization from +10 mV to -60 mV was significantly decreased from 15.4 +/- 2.4 to 6.8 +/- 1.4 nA (P less than 0.01, n = 6) and the deactivation time constant significantly increased by 20.7% (P less than 0.01, n = 6). The steady-state activation curve for IK was shifted in the hyperpolarized direction by 6.9 +/- 2.9 mV, suggesting a potent voltage-dependent block of this current by aprindine. The hyperpolarization-activated inward current (Ih) was decreased from 14.4 +/- 5.4 to 12.0 +/- 5.5 nA (P less than 0.05, n = 5). The transient outward and inward currents induced by 1 mumol/l acetylstrophanthidin were almost completely suppressed after the addition of 1 mumol/l aprindine. These results suggest that aprindine exerts a negative chronotropic action both by slowing deactivation of IK and by reducing Isi and Ih, and delays atrioventricular nodal conduction by reducing Isi and IK. These blocking actions of aprindine together with its inhibition of the transient outward and inward currents may explain its antiarrhythmic effects on the atrioventricular node.

Action Potentials↗
PubMed1981

[Comparison of the efficacy of aprindine and quinidine in chronic ventricular rhythm disorders].

The object of this study was to compare the efficacity and the side effects of Aprindine and Quinidine in patients with stable ventricular arrhythmias. A series of 33 patients with chronic stable ventricular arrhythmias were given successively Aprindine and Quinidine on the principle of extrasystoles (VES) determined by computer analysis of Holter recordings. The VES were counted every hour and the statistical study used analysis of variance followed by linear contrast and also the sign test. The stability of the arrhythmia was verified by several control Holter recordings without therapy (average : 3,3 per patient). Low dose regimes were used in 17 patients (an average of 50 to 60mg/day Aprindine, and 481 mg Quinidine base), and Quinidine was shown to be the more active (p less than 0.05 to 0.003 according to the test used), reducing the number of VES by 39% compared to an average of 21% for Aprindine. In the other 16 patients with a higher dosage regime, 109 mg Aprindine and 707 mg Quinidine base, there was no significant difference between Quinidine and Aprindine (p less than 0.08 to 0.12), Quinidine reducing the number of VES by an average of 54%, and Aprindine by 36%. Quinidine caused diarrhoea in I patient on the low dose and 4 patients in the high dose regime. Aprindine caused neurological side effects in 2 patients on the low dose, and 7 patients on the high dose regime. Aprindine at 100 mg/day may therefore be used in the same manner as Quinidine at usual dosages as regards the incidence of side effects of the two drugs. However, the ratio of effective dose/toxic dose is lower with Aprindine than with Quinidine.

Aprindine↗
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↗
PubMedDate not supplied

Aprindine inhibits calmodulin-stimulated phosphodiesterase and Ca-ATPase activities.

Aprindine, an antiarrhythmic agent with structural similarities to lidocaine and procainamide, has proved effective in treatment of patients with ventricular premature depolarizations, ventricular tachycardia, and supraventricular arrhythmias. While its effects at an electrophysiologic level have been elucidated, its mechanism of action at a biochemical level has remained largely undefined. The data in this communication demonstrate that aprindine inhibits the activation of bovine brain cyclic 3':5'-nucleotide phosphodiesterase (EC 3.1.4.17) by calmodulin. This inhibition is specific for the calmodulin-stimulated enzyme, as no effect of aprindine is seen when phosphodiesterase is assayed in the absence of calmodulin. The inhibition is competitive with respect to substrate (cyclic AMP) and calmodulin concentrations. In the presence of 10 nM calmodulin, the ID50 for aprindine is 18 microM. This inhibition is not the result of aprindine acting as a calcium chelator because increasing the calcium concentration does not reverse the inhibitory effect. Aprindine also inhibits calmodulin-stimulated Ca-ATPase (ATP phosphohydrolase EC 3.6.1.3) activity, but again has no effect on the enzyme in the absence of calmodulin. Aprindine has hydrophobic properties which may be responsible for the inhibitory effect. Sufficient concentrations of aprindine are achieved in myocardial tissues to interfere with the ability of calmodulin to stimulate a number of enzymes present in the heart.

Animals↗
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↗
PubMedDate not supplied

Effective plasma concentrations of aprindine in canine ventricular arrhythmias.

Antiarrhythmic effects of aprindine were examined using three canine ventricular arrhythmia models (induced by digitalis, adrenaline, and two-stage coronary ligation), and the minimum effective plasma concentration of aprindine was determined for each arrhythmia model. Aprindine suppressed all three arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by digitalis, adrenaline, and 24-h and 48-h coronary ligation were 0.8 +/- 0.4, 1.0 +/- 0.4, 1.6 +/- 0.3, and 3.1 +/- 0.5 micrograms/ml, respectively (mean +/- SD, n = 6-7). The minimum effective plasma concentrations of aprindine for digitalis- and adrenaline-induced arrhythmias were significantly lower than those for coronary ligation-induced arrhythmias. Oral aprindine was also effective in suppressing both the 24- and 48-h coronary ligation-induced arrhythmias. Aprindine had a hypotensive effect when it was given intravenously, but this effect was not observed when it was given orally. The correlations between the aprindine plasma concentrations and the antiarrhythmic effects were not very strong and indicated individual variations in sensitivity to aprindine.

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↗
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↗
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↗