aconitine and Chronic-Disease

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

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

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

Qiliqiangxin capsule (QLQX), composed of 11 herbs, is an effective traditional Chinese medicine (TCM) that has been widely used for treatment of chronic heart failure (CHF) in China. In the Chinese pharmacopoeia (Ch.P.) only astragaloside was described as the marker component to control the quality of QLQX, which could not reflect the overall effectiveness.. The aim of this work was to investigate the quality markers (Q-markers) of QLQX based on the association of the pharmacodynamics (PD) of inhibitory effect on activated renin-angiotensin-aldosterone system (RAAS) and the pharmacokinetics (PK) of bioactive compounds according to the Q-marker theory.. The contents of astragaloside, calycosin-7-glucoside, sinapine, ginsenoside Rb1, ginsenoside Rb2, ginsenoside Rg1, salvianolic acid A, salvianolic acid B, danshensu, rosmarinic acid, formononetin, aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypacoitine were determined by an HPLC-MS/MS method both in QLQX preparation and in the plasma of CHF rats administered intragastrically with QLQX. The effect of lowering angiotensin II (Ang II) production by QLQX was assayed by ELISA. The association between PK and PD was explored and the bioactive compounds with higher content in vitro and better exposure in vivo, which were closely related to the inhibitory effect on the activated RAAS, were identified as Q-markers of QLQX for CHF treatment.. The contents of 17 constituents were in the order of salvianolic acid B > danshensu > ginsenoside Rb1 > sinapine > benzoylmesaconine > astragaloside > benzoylhypacoitine > ginsenoside Rb2 > salvianolic acid A > ginsenoside Rg1 > calycosin-7-glucoside > rosmarinic acid > formononetin > benzoylaconine > hypaconitine > aconitine > mesaconitine in QLQX preparation. PK and PD association study of 14 bioactive compounds of QLQX showed the maximum effect (E. Astragaloside, calycosin-7-glucoside, sinapine and ginsenoside Rg1 are suitable as the Q-markers of QLQX for CHF treatment, which have higher content in vitro, finer exposure in vivo and a direct correlation with the inhibitory effect on activated RAAS.

Topics: Aconitine; Angiotensin II; Animals; Benzofurans; Biomarkers; Chromatography, High Pressure Liquid; Chronic Disease; Drugs, Chinese Herbal; Ginsenosides; Heart Failure; Isoflavones; Male; Medicine, Chinese Traditional; Quality Control; Rats, Sprague-Dawley; Tandem Mass Spectrometry

The acetylcholine receptor-operated K(+) (KACh) channel may be a novel target for atrial-specific antiarrhythmic therapy. Recently it has been demonstrated that tertiapin, a selective blocker of KACh channel, suppressed aconitine-induced atrial fibrillation (AF) in dogs. However, the precise mechanism by which the KACh-channel blocker inhibits the aconitine-induced AF remains unknown. This study was undertaken to determine the role of KACh channel in aconitine-induced AF in guinea pigs. Tertiapin terminated the aconitine-induced AF in anesthetized guinea pigs. The results of an in vitro electrophysiological experiment using atrial cells and atrial preparations suggest that aconitine might activate KACh channels in atrial cells, probably by intracellular Na(+) accumulation, and inhibition of KACh channels by tertiapin might suppress AF by producing conduction block, probably due to further decrease in the resting membrane potential. Since it has been reported that constitutively active KACh channels can be observed in atrial cells of patients with chronic AF, aconitine-induced AF may be used as an experimental model for evaluation of drug effect on chronic AF.

Topics: Aconitine; Animals; Atrial Fibrillation; Bee Venoms; Cells, Cultured; Chronic Disease; Disease Models, Animal; Dogs; Electrocardiography; Electrophysiological Phenomena; Guinea Pigs; Heart Atria; In Vitro Techniques; Membrane Potentials; Molecular Targeted Therapy; Potassium Channel Blockers; Potassium Channels; Sodium

Clinical studies have established the role of cigarette smoking as a risk factor in the progression of chronic kidney disease (CKD). We have shown that nicotine promotes mesangial cell proliferation and hypertrophy via nonneuronal nicotinic acetylcholine receptors (nAChRs). The α7-nAChR is one of the most important subunits of the nAChRs. These studies were designed to test the hypothesis that nicotine worsens renal injury in rats with 5/6 nephrectomy (5/6Nx) and that the α7-nAChR subunit is required for these effects. We studied five different groups: Sham, 5/6Nx, 5/6Nx + nicotine (Nic; 100 μg/ml dry wt), 5/6Nx + Nic + α7-nAChR blocker methyllicaconitine (MLA; 3 mg·kg(-1)·day(-1) sq), and Sham + Nic. Blood pressure was measured by the tail-cuff method, and urine was collected for proteinuria. After 12 wk, the rats were euthanized and kidneys were collected. We observed expression of the α7-nAChR in the proximal and distal tubules. The administration of nicotine induced a small increase in blood pressure and resulted in cotinine levels similar to those found in the plasma of smokers. In 5/6Nx rats, the administration of nicotine significantly increased urinary protein excretion (onefold), worsened the glomerular injury score and increased fibronectin (∼ 50%), NADPH oxidase 4 (NOX4; ∼100%), and transforming growth factor-β expression (∼200%). The administration of nicotine to sham rats increased total proteinuria but not albuminuria, suggesting direct effects on tubular protein reabsorption. These effects were prevented by MLA, demonstrating a critical role for the α7-nAChR as a mediator of the effects of nicotine in the progression of CKD.

Topics: Aconitine; alpha7 Nicotinic Acetylcholine Receptor; Animals; Blood Pressure; Chronic Disease; Disease Models, Animal; Disease Progression; Kidney Diseases; Male; NADPH Oxidase 4; NADPH Oxidases; Nephrectomy; Nicotine; Nicotinic Antagonists; Oxidative Stress; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic; Transforming Growth Factor beta

Nicotinic receptor decreases in the frontal cortex and hippocampus are important mediators of cognitive impairment in both schizophrenia and Alzheimer's disease. Drug treatments for these diseases should take into account the impacts of compromised brain function on drug response. This study investigated the impact of compromised nicotinic receptor activity in the frontal cortex in rats on memory function. Since both Alzheimer's disease and schizophrenia can involve psychosis, antipsychotic drugs are often given. The impacts of antipsychotic drugs on cognitive function have been found to be quite variable. It is the hypothesis of this and previous studies that the cognitive effects of antispychotic drugs on cognitive function depend on the integrity of brain systems involved in cognition. Previously in studies of the hippocampus, we found that chronic inhibition of beta2-containing nicotinic receptors with dihydro-beta-erythrodine (DHbetaE) impaired working memory and that this effect was attenuated by the antipsychotic drug clozapine. In contrast, chronic hippocampal alpha7 nicotinic receptor blockade with methyllycaconitine (MLA) potentiated the clozapine-induced memory impairment which is seen in rats without compromised nicotinic receptor activity. The current study determined medial frontal cortical alpha7 and beta2-containing nicotinic receptor involvement in memory and the interactions with antipsychotic drug therapy with clozapine. Chronic DHbetaE and MLA infusion effects and interactions with systemic clozapine were assessed in female rats tested for memory on the radial-arm maze. Antipsychotic drug interactions with chronic systemic nicotine were investigated because nicotinic procognitive treatment has been proposed. The same local infusion DHbetaE dose that impaired memory with hippocampal infusion did not impair memory when infused in the medial frontal cortex. Frontal DHbetaE infusion potentiated clozapine-induced memory impairment, whereas previously the memory impairment caused by hippocampal DHbetaE infusion was attenuated by clozapine. Frontal cortical MLA infusions at a dose that previously was found to potentiate the clozapine-induced memory impairment with hippocampal infusion had no significant effect when infused into the medial frontal cortex. The location and subtype of nicotinic receptor underactivity are critical determinates for clozapine effects on memory. Patients with hippocampal beta2-containing nicotinic receptor loss may

Topics: Aconitine; alpha7 Nicotinic Acetylcholine Receptor; Animals; Antipsychotic Agents; Cerebral Cortex; Chronic Disease; Clozapine; Dihydro-beta-Erythroidine; Female; Maze Learning; Memory Disorders; Memory, Short-Term; Microinjections; Nicotinic Antagonists; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic

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

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