aconitine and allapinin

Antiarrhythmic drug allapinin has been used in clinical practice for a long time but data of investigation of its effects and mechanism of action are scanty. The aim of this review is to summarize results of clinical studies of allapinin supplementing them with personal unpublished data. The review embraces pharmacokinetics and pharmacodynamics of the drug, its efficacy in the treatment of various cardiac rhythm disturbances and side effects. The conclusion is made that clinical application of allapinin as class 1C antiarrhythmic drug according to Vaughan-Williams classification should be guided by general recommendations concerning indications and contraindications for this class of antiarrhythmic drugs. Special feature of allapinin is its high efficacy for prevention of attacks of paroxysmal atrial fibrillation.

Topics: Aconitine; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Trials as Topic; Humans; Treatment Outcome

Topics: Aconitine; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Disopyramide; Electrocardiography; Humans; Moricizine; Phenothiazines; Procainamide; Propranolol

To assess and compare the safety and efficacy of allapinine and quinidine bisulphate in the treatment of patients with persistent atrial fibrillation after cardioversion. Design--Prospective, randomised, open study. Patients--73 consecutive patients (men only, mean age 44 ± 11 years) with persisnent atrial fibrillation and flutter. Interventions--37 patients were randomised to allapinine (ALP) (1.5 mg/kg/d), 36 to quinidine bisulphate (QUIN) (15 mg/kg/d) with subsequent successful pharmacological or electrical cardioversion. Main outcome measures--Recurrence of atrial fibrillation or side effects.. In the ALP group 15 of the 37 patients developed atrial fibrillation up to 12 month of follow-up, while in the QUIN group 20 patients developed atrial fibrillation and 5 experienced significant side effects. Relative risk (RR) (ALP vs QUIN) 0.58 (95% CI 0.37-0.91, p < 0.02). The number needed to treat (NNT) was (-3.48) (14.2-1.97 harm). When 5 patients with significant side effects were excluded from the analysis RR was 0.62 (95% CI 0.39-1.0, p = 0.052) and NNT--(-4.1) (122.7-2.1 harm) but power of the study was too low--67%.. Allapinine is as effective as quinidine bisulphate in the long term treatment of patients with persistent atrial fibrillation after successful cardioversion but causes significantly less side effects.

Topics: Aconitine; Adult; Anti-Arrhythmia Agents; Atrial Fibrillation; Drug Monitoring; Electric Countershock; Humans; Male; Middle Aged; Quinidine; Recurrence; Time; Treatment Outcome

Cross-over trial studied comparative effectiveness and tolerance of allapinine, rhythmonorm and isoptine in patients with paroxysmal supraventricular tachycardia (PSVT). Treatment effects did not differ much. Analysis of the preventive efficiency of the above drugs with reference to PSVT form has demonstrated that in paroxysmal atrioventricular reciprocal tachycardia the highest activity was shown by isoptine and rhythmonorm, in paroxysmal orthodromic reciprocal tachycardia--by rhythmonorm and allapinin. In long-term therapy, a preventive effects of allapinin, rhythmonorm and isoptine achieved at short-term course therapy persisted in 90.9, 95.6 and 81.5% patients, respectively. All the above drugs cause moderate inhibition of atrioventricular and intraventricular conduction. Isoptin had the best tolerance.

Topics: Aconitine; Adolescent; Adult; Aged; Anti-Arrhythmia Agents; Cross-Over Studies; Female; Humans; Male; Middle Aged; Tachycardia, Paroxysmal; Tachycardia, Supraventricular; Verapamil

Platelet aggregability was studied in 81 patients with prior myocardial infarction with various cardiac arrhythmias and its effects of some antiarrhythmic agents (allapinine, ethacizine, obsidan and cordarone). It was 32-39% higher in patients with frequent ventricular extrasystole (VE) and VE of high grades (4a and 4b by the classification of Lown and Wolt) than in control patients (without arrhythmias) and patients with supraventricular and rare VE. Ethacizine and cordarone produced a significant inhibitory effects on platelet functional activity, but the effects of allapinine and obsidan on this parameter were insignificant. There was no correlation between the magnitude of antiarrhythmic effects of the drugs and their antiaggregatory properties. It was shown that the results of examining the effects of antiarrhythmic agents on platelet aggregability in vitro were not in agreement with those obtained in vivo.

Topics: Aconitine; Adult; Amiodarone; Anti-Arrhythmia Agents; Cardiac Complexes, Premature; Heart Rate; Humans; Male; Middle Aged; Phenothiazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Propranolol; Tachycardia, Supraventricular

Topics: Aconitine; Aconitum; Arrhythmias, Cardiac; Biological Availability; Clinical Trials as Topic; Humans; Tablets

Echocardiographic study was performed in 24 patients with persistent atrial fibrillation (PAF) without clinical signs of circulatory failure. When treated with allapinin , all the patients with PAF showed a significant increase in heart rate (HR) and cardiac output (CO) and a decrease in total peripheral vascular resistance (TPVR). No substantial changes in the major hemodynamic parameters were found in patients with higher left ventricular dimensions; however, a significant rise in end systolic volume (ESV) was noted. There was significantly lower HR, diminished ESV, higher stroke volume and increased CO, elevated ejection fraction and TPVR with sinus rhythm. In PAF patients without apparent signs of circulatory failure, hemodynamic effects of allapinin may be accounted for by its direct vasodilatory action on the arterial bed and by its ability to affect cardiac autonomic innervation. A moderate cardiodepressive effect of the agent may be reflected by deteriorated latent signs of myocardial incompetence which are levelled off following sinus rhythm recovery.

Topics: Aconitine; Aconitum; Adult; Anti-Arrhythmia Agents; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Hemodynamics; Humans; Male; Middle Aged; Sinoatrial Node; Stimulation, Chemical; Tablets

Effect of a new antiarrhythmic drug allapinin was studied in 21 patients with chronic ventricular extrasystoles by an acute drug test with single oral dose of the drug controlled by 12-hour Holter monitoring. In 9 cases the dose was 50 mg. Maximal total reduction of ventricular ectopic complexes (VEC) per hour was 67 +/- 28% (mean value); in 5 cases (55%) it exceeded 90% of basal level. At peak of action, PQ interval increased by 15%, QRS--by 14%, QT was not significantly changed. In 14 cases the dose was 75 micrograms. Maximal VEC number reduction per hour was on the average 89 +/- 18% and in 12 cases (88%) exceeded 90%. PQ increased by 22%, QRS--by 23% and QT by 9% though JT was not changed (average peak values). It is thus concluded that single oral dose of allapinin has pronounced antiarrhythmic effect in patients with VEC and influences ECG intervals in the way characteristic for class IC antiarrhythmic drugs. The degree of the effect depends on the dose.

Topics: Aconitine; Aconitum; Administration, Oral; Adult; Cardiac Complexes, Premature; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Heart Ventricles; Humans; Male; Middle Aged

Allapinine (Class IC), a new antiarrhythmic agent, was studied in 76 patients with premature contraction. Allapinine was found to be beneficial both in ventricular and supraventricular premature beats. Oral allapinine usually showed its effect 40-60 minutes following its administration, its maximum action being 4-5 hours later, its duration was some 8 hours. The optimal dose of the drug amounted to 75 mg/day. Larger-dose allapinine produced adverse effects, its lower dosage had no antiarrhythmic effect. The drug failed to affect blood pressure, heart rate, QT interval length. The PQ interval and QRS complex were increased. The side effects were dose-dependent. There was a risk of the drug's arrhythmogenic effect.

Topics: Aconitine; Aconitum; Adolescent; Adult; Cardiac Complexes, Premature; Clinical Trials as Topic; Diplopia; Dizziness; Dose-Response Relationship, Drug; Female; Hemodynamics; Humans; Male; Middle Aged

Allapinin after i.v. bolus infusion in a dose of 30 mg is relatively quickly eliminated from blood (in patients without congestive heart failure half-elimination period is 2.4 +/- 0.5 h and clearance is 79.0 +/- 8.9 l/h) which makes a good reason for its intravenous infusion according to the scheme "load dose + drop infusion". Marked heart failure in patients with acute myocardial infarction compared to patients without heart failure results in reduced elimination rate, decreased clearance, significantly increased plasma allapinin concentration which should be taken in account when choosing the regime of drug infusion. The elimination of allapinin is mainly metabolic and not renal (only about 17% of the drug is excreted with urine).

Topics: Aconitine; Aconitum; Adult; Aged; Clinical Trials as Topic; Female; Half-Life; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction; Ventricular Fibrillation

Clinical assessment of a new antiarrhythmic drug, allapinin, was carried out in 42 patients with chronic ventricular extrasystoles. Single intravenous doses were effective where they exceeded 0.32 mg/kg. Doses above 0.42 mg/kg were regularly associated with side effects, such as dizziness or, less commonly, diplopia. The 0.39 mg/kg dose produced an antiarrhythmic effect in 61% of patients, whose PQ interval was lengthened by 23%, and the QRS complex, by 18%, while QTc duration remained unchanged. Heart rate and arterial blood pressure were virtually unchanged, either. The peak of antiarrhythmic effect fell to the second postadministration hour, and the effect persisted within an average of 7.6 hours. Therefore, allapinin appears to be a potent quinidine-like agent.

Topics: Aconitine; Adolescent; Adult; Aged; Anti-Arrhythmia Agents; Cardiac Complexes, Premature; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Heart Conduction System; Heart Ventricles; Humans; Injections, Intravenous; Male; Middle Aged

The efficiency of a number of antiarrhythmic drugs (etmozin, quinidine, mexytil, allapinin, cordarone), used alone and in combinations, was assessed in 13 patients with refractory continuous extrasystoles of varying origins. Antiarrhythmic effect of the drugs was evaluated by means of Holter ECG monitoring. Monotherapies were only effective in 3 patients, and developing side effects limited the possibilities of long-term use. Combined treatment produced a greater effect, while smaller doses of individual drugs making up the combination resulted in a better tolerance due to reduced side effects.

Topics: Aconitine; Adult; Anti-Arrhythmia Agents; Cardiac Complexes, Premature; Clinical Trials as Topic; Drug Resistance; Drug Therapy, Combination; Female; Humans; Male; Mexiletine; Middle Aged; Moricizine; Phenothiazines; Quinidine

Antiarrhythmic efficacy of allapinin was assessed in 15 patients with heart failure combined with ventricular arrhythmias (48 h ECG monitoring). The drug was administered against a background of maintenance therapy with digoxin at a daily dose of 75 mg (digoxin concentration in blood plasma was 1.51 +/- 0.12 ng/ml). The drug was shown to possess marked antiarrhythmic activity causing a decrease of the total number of ventricular extra systoles by an average of 72.3%, group ventricular extrasystoles--by 84.5%. The drug can be recommended in combination with cardiac glycosides to patients with severe heart failure combined with ventricular arrhythmias.

Topics: Aconitine; Aconitum; Adult; Cardiac Complexes, Premature; Cardiac Output; Cardiac Output, Low; Clinical Trials as Topic; Heart Ventricles; Humans; Middle Aged

Topics: Aconitine; Aconitum; Adult; Aged; Anti-Arrhythmia Agents; Cardiac Complexes, Premature; Clinical Trials as Topic; Disopyramide; Female; Humans; Male; Mexiletine; Middle Aged; Moricizine; Phenothiazines; Placebos; Propranolol; Quinidine

A double blind randomized cross-over study was conducted to analyze antiarrhythmic activity of the new Soviet drugs allapinin , ethacizine in comparison with mexitil. Altogether 33 patients with ventricular disorders of cardiac rhythm of high gradations after Lown B. were investigated including patients with paroxysmal ventricular tachycardia. The authors managed to establish and compare the group antiarrhythmic efficacy and safety of each drug, and to assess a degree of selective efficacy of each of them.

Topics: Aconitine; Aconitum; Adolescent; Adult; Aged; Anti-Arrhythmia Agents; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Female; Humans; Male; Mexiletine; Middle Aged; Phenothiazines; Random Allocation; Tachycardia, Ectopic Junctional; Tachycardia, Paroxysmal; Tachycardia, Supraventricular

Topics: Aconitine; Aconitum; Administration, Oral; Arrhythmias, Cardiac; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Injections, Intravenous; Placebos

The results of the trial point to a potent and protracted antiarrhythmic effect of allapinin equally pronounced with both intravenous and oral administration to patients with ventricular and supraventricular premature beats. The side effects of the drug in acute tests and during short-term course therapy are not significant.

Topics: Aconitine; Adolescent; Adult; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Trials as Topic; Electrocardiography; Female; Heart Rate; Humans; Injections, Intravenous; Male; Middle Aged; Monitoring, Physiologic; Tablets; Time Factors

Lappaconitine Hydrobromide (LH, allapinin) has been included by authors of National Guidelines on Diagnosis and Treatment of Atrial Fibrillation (AF), 2012 in the number of medications recommended for use in patients with AF for rhythm control. Moreover, LH is also included into the List of Vital and Essential Medicinal Drugs (VEMD) 2015. However, LH is not mentioned in corresponding guidelines of the European Society of Cardiology (ESC). Aim of the present review was to explore evidence base underlining use of LH in the context of AF and to understand reason for LH-related discrepancy between European and domestic guidelines.. Literature search has indicated that efficacy of LH was assessed only in small open studies. None of prospective trials included more than 100 patients. For more than 25 years of presence on the market slightly more than 400 patients were administered LH in clinical studies. In the only trial, designated as randomized number of participants (only men younger than 60 years) was small and the comparator was quinidine that presently is not used for maintenance of sinus rhythm in AF. Another study referenced in domestic guidelines on management of AF was observational and not intended for comparison of antiarrhythmic activity of drugs.. Design of studies reviewed as well as their results provide insufficient evidence supporting the use of LH for maintenance of sinus rhythm in routine management of AF. At present inclusion of LH in guidelines on AF management and in the List of VEMD appears unjustified.

Topics: Aconitine; Anti-Arrhythmia Agents; Atrial Fibrillation; Evidence-Based Practice; Humans; Male; Prospective Studies

Allapinin, class 1C antiarrhythmic drug, is highly effective in treatment of patients with ventricular premature beats (VPB). The purpose of work was retrospective assessment of efficacy and safety of allapinin in patients with benign ventricular arrhythmias. 73 patients with VPB and no structural heart disease were selected from a database. In short course allapininin in dose of 75-150 mg per os daily decreased the number of VPB for more than 90% in 46,6% of patients. In 34,4% cases tolerable drug side effects were observed. Among patients with VPB burden of 10% and higher allapinin reduced this quantity below the indicated value in 76% of cases with tolerable drug side effects in 38,6% of cases. In long treatment study antiarrhythmic effect of allapinin persisted and no other side effects of the drug were documented.. Allapinin is highly effective in treatment of patients with VPB without structural heart disease.

Topics: Aconitine; Adolescent; Adult; Anti-Arrhythmia Agents; Drug Administration Schedule; Electrocardiography; Female; Humans; Male; Middle Aged; Ventricular Premature Complexes; Young Adult

Tachyarrhythmias (TA) - dangerous postoperative complications of coronary artery bypass grafting, threatening the lives of patients and found, according to different authors, in 13-40% of cases. VFS - an antiarrhythmic drug that belongs to a class 1C, is effective in the treatment and prevention of a variety of cardiac arrhythmias. The aim of the work was to study the clinical efficacy of VFS CHD patients with a history of tachyarrhythmias during the perioperative period of coronary bypass surgery, as well as its comparison with other antiarrhythmic drug (amiodarone). Clinical efficacy was evaluated in 218 patients with coronary heart disease at baseline with a history of tachyarrhythmia (paroxysmal atrial fibrillation or premature ventricular high grade (IV and V class on classification of Lown B. and Wolf M. in the modification of Ryan M.). Shown that the VFS is more effective than amiodarone, both in paroxysmal atrial fibrillation and ventricular arrhythmias when high gradation.

Topics: Aconitine; Amiodarone; Anti-Arrhythmia Agents; Chemoprevention; Comparative Effectiveness Research; Coronary Artery Bypass; Coronary Artery Disease; Female; Heart Rate; Humans; Male; Middle Aged; Perioperative Care; Postoperative Complications; Retrospective Studies; Tachycardia; Treatment Outcome

Antiarrhythmic therapy of patients with disturbed automatism of the sinus node and impaired atrioventricular conductance may be complicated by hemodynamically significant bradycardias and contraindications for implantation of a cardiac electrical stimulator This study aimed at estimating effect of antiarrhythmic therapy with allapinin on the function of sinus and atrioventricular nodes. It included 20 patients (mean age 37.5+-2.3 years) with disturbed cardiac rhythm and sinus node dysfunction treated with allapinin (37.5 - 50 mg/d per os). This therapy had well apparent antiarrhythmic effect manifest as improvement of supraventricular and ventricular ectopic activities in the absence of negative influence on the function of sinus and atrioventricular nodes.

Topics: Aconitine; Adult; Anti-Arrhythmia Agents; Bradycardia; Depression, Chemical; Dose-Response Relationship, Drug; Drug Monitoring; Electrocardiography, Ambulatory; Electrophysiologic Techniques, Cardiac; Female; Heart Conduction System; Heart Rate; Humans; Male; Sick Sinus Syndrome; Tachycardia, Paroxysmal; Treatment Outcome; Ventricular Premature Complexes

Intravenous glialin in a dose of 7 mg/kg suppressed the number of ectopic contractions caused by double ligature of the left coronary artery by the method of Harris and almost 2-fold prolonged animal life-span in comparison with the control. The maximum antiarrhythmic effect of glialin developed after 180 min and persisted for 5 h. Glialin injected intravenously (10 mg/kg) after myocardial infarction under conditions of programmed electrical stimulation inhibited conduction of evoked impulse in the atria, Purkinje fibers, and ventricular myocardium and did not modify the effective refractory periods of the atria and ventricles.

Topics: Aconitine; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Dogs; Electrophysiology; Glycyrrhizic Acid; Heart Conduction System; Myocardial Infarction

Antiarrhythmic activity of oral allapinin was studied in 64 patients with ischemic heart disease. 27 of the patients had undergone coronary artery bypass grafting 2 to 12 months before, 19 patients had postinfarction cardiosclerosis, 38--arterial hypertension, 30--circulation insufficiency stage I. Arrhythmia presented as ventricular extrasystole (n = 28), paroxysmal atrial fibrillation (n = 18), paroxysmal atrial tachycardia (n = 11), frequent supraventricular extrasystole (n = 7). Arrhythmia continued from 6 months to 8 years. An effective single dose was defined with acute pharmacological test. The treatment course lasted for 21 days. Allapinin proved to be highly effective: ventricular ectopic activity was suppressed in 71.4% patients, atrial tachycardia paroxysms were prevented in 72.7%, paroxysms of atrial fibrillation--in 77.8%. Allapinin tolerance was good. Extracardiac side effects occurred most frequently, but dose lowering was necessary only in 6.2%. The drug was discontinued because of cardiac side effects in 4.7% cases. ECG monitoring is a highly informative method of the treatment efficacy control.

Topics: Aconitine; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Artery Bypass; Drug Tolerance; Electrocardiography; Humans; Hypertension; Male; Middle Aged; Monitoring, Physiologic; Myocardial Ischemia; Time Factors

Topics: Aconitine; Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Cats; Electric Stimulation; Electrocardiography; Periodicity; Vagus Nerve

The antiarrhythmic effects of allapinine were studied in 57 patients with chronic circulatory failure (CCF) and cardiac arrhythmias by employing 48-hour Holter monitoring. Allapinine was found to suppress premature ventricular contraction, group premature ventricular contraction and 'runs' of ventricular tachycardia by 82.5, 88.6, and 93.1%, respectively. The antiarrhythmic activity of the agent was more pronounced in patients with coronary heart disease, Stages I-IIA CCF and left ventricular ejection fraction greater than 40%. In addition, in Stages I-IIA CCF allapinine increased myocardial contractility and left ventricular ejection fraction, whereas in Stages IIB-III CCF it showed a slight cardiodepressive effect. Thus, when given in the course therapy in patients with CCF, allapinine has a high antiarrhythmic activity and, to a lesser extent, affects central hemodynamics.

Topics: Aconitine; Adult; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiomyopathy, Dilated; Coronary Disease; Electrocardiography, Ambulatory; Female; Heart Diseases; Heart Valve Diseases; Hemodynamics; Humans; Male; Middle Aged

Single intravenous allapinine, 30 mg, given to patients with acute myocardial infarction, including those with moderate circulatory insufficiency, fails to affect central hemodynamic parameters or has a favourable action: normalizes pulmonary diastolic pressure, cardiac index, diminishes total peripheral vascular resistance. The agent also produces a weak antihypertensive effect and increases heart rate.

Topics: Aconitine; Adult; Anti-Arrhythmia Agents; Female; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction

Out of 85 patients with cardiac arrhythmias in the presence of chronic coronary heart disease, 28 who were resistant to ethacisine and allapinine were included into the study. They had frequent and persistent arrhythmias. The patients were divided into 2 groups: (1) the patients receiving intravenous He-Ne laser therapy in combination with one of the above drugs; (n = 17) and (2) those taking He-Ne laser therapy alone (n = 11). The efficacy of the therapies were controlled by 24-hour monitoring. An antiarrhythmic effect was more frequently observed when He-Ne laser was combined with one of the above drugs than when it was given alone (67.4 and 36.3%, respectively).

Topics: Aconitine; Adult; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Disease; Drug Resistance; Helium; Humans; Laser Therapy; Middle Aged; Neon; Phenothiazines

During a prolonged (24-hour) intravenous administration in a dose of 126 mg, allapinine produced a stable pronounced antiarrhythmic effect in 90% of the patients with frequent premature ventricular contraction and adverse reactions in the central nervous system in 65% of the cases. However, the latter effect of allapinine is short-term and ceased independently without altering the infusion rate. More serious adverse effects (hypotensive reactions, proarhythmic effects) occurred in 4% of the cases.

Topics: Aconitine; Adult; Aged; Anti-Arrhythmia Agents; Cardiac Complexes, Premature; Chronic Disease; Coronary Disease; Female; Humans; Infusions, Intravenous; Male; Middle Aged

Doppler echocardiography is an excellent tool to study the hemodynamic effects of cardiac drugs. Resting and exercise effects produced by metoprolol and allapinin on Doppler-derived measures of left ventricular (LV) performance were examined in patients with paroxysmal supraventricular tachycardias. Seventeen patients underwent continuous wave Doppler examination from the suprasternal notch at rest and during each stage of a standard exercise protocol. The study was repeated following 3-4 days of treatment with metoprolol given in a daily dose of 200 mg. The hemodynamic effects of allapinin, 100 mg daily, were evaluated in the same manner in 8 patients. With metoprolol, all resting Doppler measurements were altered insignificantly and all Doppler--derived parameters of aortic flow (peak, velocity, mean acceleration, cardiac index and LV ejection force) were much lower at the maximum exercise. Allapinin failed to alter any Doppler measurements of aortic blood flow at rest or during the peak exercise.

Topics: Aconitine; Adolescent; Adult; Echocardiography, Doppler; Exercise Test; Hemodynamics; Humans; Metoprolol; Middle Aged; Rest; Tachycardia, Paroxysmal; Tachycardia, Supraventricular

Data are reported of a study of the efficacy of membrane-stabilizing antiarrhythmic agents--ethmosin, ethacisin, allapinin. The latter was used in the treatment of 85 patients with arrhythmias of different etiology and proved more effective as compared with ethmosin and ethacisin. In ventricular extrasystole the effect was favourable in 86%, in supraventricular--in 70% of patients.

Topics: Aconitine; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Dose-Response Relationship, Drug; Drug Evaluation; Electrocardiography; Humans; Middle Aged; Moricizine; Phenothiazines; Remission Induction

An intracardiac electrophysiological study was undertaken to examine 15 patients with paroxysmal supraventricular tachycardias. Allapinin intravenously given in a dose of 0.4 mg/kg, was tested for effects. The agent was demonstrated to cause a substantial inhibition of rapid retrograde pathway function in atrioventricular nodal tachycardia and abnormal antero- and retrograde pathway function. This is the major aspect of the drug's action that prevents the development of episodes of paroxysmal supraventricular tachycardias. The agent fails to virtually affect the function of the atrioventricular node in the anterograde direction in the two types of the tachycardia. Thus, allapinin has the mechanism of action that is typical of quinidine-like drugs used in supraventricular tachycardias.

Topics: Aconitine; Adult; Anti-Arrhythmia Agents; Atrioventricular Node; Cardiac Pacing, Artificial; Female; Humans; Injections, Intravenous; Male; Middle Aged; Tachycardia, Atrioventricular Nodal Reentry; Tachycardia, Paroxysmal

Block of sodium currents by allapinin (diterpene alkaloid with strong antiarrhythmic properties) was investigated in isolated, voltage clamped rat trigeminal neurons and cultured neonatal rat single ventricular myocytes. Allapinin produces a decrease in sodium current amplitude without any changes in voltage dependent properties. Possible differences between the mechanisms of antiarrhythmic effect of diterpene alkaloids and classic antiarrhythmic agents have been analysed.

Topics: Aconitine; Animals; Anti-Arrhythmia Agents; Calcium; Cells, Cultured; Heart; Myocardium; Neurons; Rats; Trigeminal Ganglion

Topics: Aconitine; Adolescent; Adult; Anti-Arrhythmia Agents; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Moricizine; Phenothiazines

Topics: Aconitine; Air Pollutants, Occupational; Animals; Anti-Arrhythmia Agents; Drug Industry; Embryo, Mammalian; Female; Guinea Pigs; Male; Mice; Pregnancy; Rabbits; Rats; Skin

The authors summed up the practical experience gained in long-term maintenance treatment with allapinine, a new Soviet antiarrhythmic agent, given to 65 patients with various cardiac arrhythmias in the outpatient setting. The long-term allapinine use yielded good results: its efficacy was proved to be approximately equal (63% and 60%) in patients with ventricular or supraventricular extrasystoles, respectively, but it was 77% in those with paroxysmal atrial fibrillation. There were no decreases in antiarrhythmic activity of allapinine during its long-term therapy. The agent produced no significant effects on heart rate, blood pressure, and myocardial contractility. Its side effects were recorded in 17 (26.2%) patients, however, withdrawal of the agent was required only in 6 cases.

Topics: Aconitine; Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Female; Humans; Male; Middle Aged; Time Factors

Block of sodium currents by allapinine (diterpene alkaloid with strong antiarrhythmic properties) was investigated in isolated, voltage-clamped trigeminal neurons of a rat and single ventricular myocytes of a neonatal rat. Allapinine (in micromolar concentrations) produced a 70-90% decrease of the sodium current amplitude without any changes in voltage-dependent properties of INa in both neurons and cardiomyocytes. Allapinine also blocked the aconitine-modified sodium current. An increase of depolarization frequencies (0.5 to 5.0 Hz) produced no additional block of sodium currents in allapinine-bathed neurons and ventricular myocytes.

Topics: Aconitine; Aconitum; Animals; Anti-Arrhythmia Agents; Heart; In Vitro Techniques; Membrane Potentials; Microelectrodes; Myocardium; Neurons; Ranidae; Rats; Sodium Channels; Trigeminal Ganglion

In atrial fibrillation, allapinine was shown to enhance rhythm by 7% and to increase cardiac output (p less than 0.05), as well as to slightly lower mean blood pressure and peripheral vascular resistance at rest. With exercise, both in atrial fibrillation, and sinus rhythm, there was a decrease in end-diastolic and end-systolic volumes of the left ventricle (p less than 0.05), a slight drop in ventricular ejection, that was statistically significant only with sinus rhythm (p less than 0.05). Physical exercise was not followed by an apparent additional aggravation of myocardial contractility, which makes allapinine preferable for long-term application to preserve sinus rhythm in patients without evident signs of heart failure.

Topics: Aconitine; Adolescent; Adult; Anti-Arrhythmia Agents; Atrial Fibrillation; Echocardiography; Exercise Test; Hemodynamics; Humans; Male; Middle Aged

Topics: Aconitine; Adult; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Electrocardiography; Exercise; Heart; Humans; Male; Middle Aged

The cardiorespiratory system was studied comprehensively in 27 patients with permanent atrial fibrillation (PAF) without the clinically marked signs of circulatory failure. After allapinine treatment 15 patients with bronchial obstruction manifestations demonstrated, in the presence of lasting PAF, a significant increase of the forced expiration capacity per s and of the maximum volumetric expiration rates. The data obtained may attest to the fact that the drug has beta-stimulating properties, confirming the reported evidence.

Topics: Aconitine; Adult; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Bronchodilator Agents; Cardiovascular Diseases; Chronic Disease; Humans; Male; Middle Aged; Respiration; Respiratory Function Tests

Pharmacokinetics of allapinin tablets, used as a single dose, alone or in combination with other antiarrhythmic drugs (cordarone, mexitil, ritmilen) were assessed in 11 patients with frequent extrasystoles. Allapinin pharmacokinetic pattern was basically similar in patients in whom it was very effective and those in whom it had no effect. Combined use of the above-mentioned antiarrhythmic drugs and allapinin did not affect the latter's pharmacokinetic parameters. Allapinin pharmacokinetics can be described using a one-part model.

Topics: Aconitine; Aconitum; Cardiac Complexes, Premature; Dose-Response Relationship, Drug; Humans; Tablets; Tachycardia, Supraventricular; Time Factors

The authors analyzed the density of beta 2-adrenoreceptors, their affinity for catecholamines and activity of peripheral lymphocyte adenylate cyclase in healthy donors and patients with frequent ventricular premature contraction (VPC) in their pretreatment state and during short-term ethmosine or allapinine therapy. The density of beta 2-adrenoreceptors was increased by 43%, whereas guanylimidodiphosphate- or forskolin-induced stimulation of adenylate cyclase was decreased in the lymphocytes of VPC patients as compared to those of healthy donors. Ethmosine therapy failed to produce any changes in the density and affinity of the receptors for catecholamines. Allapinine caused a 47% reduction in beta 2-adrenoreceptor density and a 10(2)-10(3)-fold decrease in receptor affinity for 1-isoproterenol. After discontinuation of allapinine, the changes in beta 2-adrenoreceptor density and affinity for catecholamines remained on days 3 and 7, respectively. The clinical effect of both ethmosine and allapinine was accompanied by an increase in lymphocyte adenylate cyclase activity.

Topics: Aconitine; Aconitum; Adenylyl Cyclases; Adult; Cardiac Complexes, Premature; Enzyme Activation; Humans; Lymphocytes; Male; Middle Aged; Moricizine; Phenothiazines; Receptors, Adrenergic, beta

Twenty one patients with various forms of paroxysmal supraventricular tachycardias (SVT) were treated with allapinine, a new antiarrhythmic drug. Intravenous infusion of allapinine (0.43 mg/kg) arrested the episodes of SVT in none of 7 patients. Oral administration of the drug for short-term treatment (150 mg/day) prevented the artificial induction or spontaneous occurrence of paroxysms in 10 of 16 patients. Thus, the first experience with allapinine shows its potential efficacy in the prophylactic treatment of paroxysmal SVT.

Topics: Aconitine; Aconitum; Adult; Anti-Arrhythmia Agents; Cardiac Pacing, Artificial; Drug Evaluation; Electrocardiography, Ambulatory; Female; Humans; Male; Middle Aged; Tachycardia, Paroxysmal

Topics: Aconitine; Adult; Anti-Arrhythmia Agents; Cardiac Complexes, Premature; Drug Evaluation; Drug Therapy, Combination; Drug Tolerance; Electrocardiography; Female; Humans; Male; Mexiletine; Middle Aged; Moricizine; Phenothiazines; Quinidine

Topics: Aconitine; Adult; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Male; Mexiletine; Middle Aged; Moricizine; Phenothiazines; Propranolol

The effect of allapinin on atrioventricular conductivity was assessed at intracardiac electrophysiologic investigation in 11 patients with various heart rhythm disorders. The effect of a 30 mg intravenous dose of the drug was evaluated 60 min after the injection. Allapinin significantly lengthened the P-Q interval and expanded the QRS complex. The effect was associated with a 24% increment in the P-A interval, a 7% increment in the A-H interval and a 31% increment in the H-V interval, suggesting that allapinin can be regarded as belonging to the first class of antiarrhythmic agents by Vaughan Williams' classification. Allapinin also shortened effective refractory time of the atrium and the atrioventricular node, as well as the total refractory period of the His-Purkinje system. Ventricular refractory periods were also shortened insignificantly. The drug is therefore assumed to have a vagolytic or, perhaps, sympathomimetic action.

Topics: Aconitine; Aconitum; Adolescent; Adult; Arrhythmias, Cardiac; Atrioventricular Node; Drug Evaluation; Electric Stimulation; Female; Heart Conduction System; Humans; Male; Middle Aged

The effect of antiarrhythmic drugs, ritmilen and allapinin, on endogenic prostanoid and cyclic nucleotide levels was examined in patients with heart rhythm disorders. Intravenous administration of antiarrhythmic agents is shown to be accompanied with increased release of prostacyclin that has antiarrhythmic properties into myocardial outflow. Both ritmilen and allapinin promoted the predominance of prostacyclin over thromboxane, with its intrinsic arrhythmogenic properties. Ritmilen- or allapinin-induced changes in prostaglandins E and F2 alpha consisted in that PGE prevailed, as compared to PGF2 alpha. There were no significant changes in cyclic nucleotide ratios (cAMP/cGMP) in response to treatment.

Topics: Aconitine; Adult; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cyclic AMP; Cyclic GMP; Dinoprost; Disopyramide; Female; Humans; Male; Middle Aged; Nucleotides, Cyclic; Prostaglandins; Prostaglandins E; Prostaglandins F; Stimulation, Chemical

The effect of Ritmilen and allapinin, a new Soviet antiarrhythmic drug, on hemodynamics and myocardial contractility were evaluated in 36 patients with various heart rhythm disorders during diagnostic coronary angiography. Ritmilen has been shown to have an essential cardiodepressive effect. An intravenous 150 mg dose of Ritmilen results in a depression of dp/dtmax, Veragut's index, ejection fraction, mean standard circular fibre shortening rate, and increase in left ventricular systolic and end diastolic pressure, total peripheral resistance and mean arterial blood pressure. Allapinin (30 mg) has no marked cardiodepressive effect, as compared to Ritmilen.

Topics: Aconitine; Adult; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Depression, Chemical; Disopyramide; Drug Evaluation; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Contraction