Potent Antiarrhythmic Agent Research Articles

Backbone-Determined Antiarrhythmic Structure-Activity Relationships for a Mirror Image, Oligomeric Depsipeptide Natural Product.

Cyclic oligomeric depsipeptides (COD) are a structural class within naturally occurring compounds with a wide range of biological activity. Verticilide is a COD (24-membered ring) that was identified by its inhibition of insect ryanodine receptor (RyR). We have since found that the enantiomer of verticilide (ent-verticilide, 1) is a potent inhibitor of mammalian RyR2, a cardiac calcium channel, and therefore a potential antiarrhythmic agent. Oddly, nat-verticilide does not inhibit RyR2. To further develop ent-verticilide as an antiarrhythmic, we explored potential SAR through systematic modification of the ester's functionality to both N-H and N-Me amides. The syntheses of these ent-verticilide-inspired analogs are detailed using a monomer-based platform enabled by enantioselective catalysis. Two analogs among 23 exhibited measurable reduction of calcium sparks in a functional assay of RyR2 activity. These findings illustrate the value of natural product-inspired therapeutic development, but the less-studied approach where the non-natural enantiomeric series harbors important SAR.

Novel pyridyl-substituted nitronyl nitroxides as potential antiarrhythmic and hypotensive agents with low toxicity and enhanced stability in aqueous solutions

This study explores the antiarrhythmic and hypotensive potential of pyridyl-substituted nitronyl nitroxides derivatives, uncovering the crucial role of a single carbon moiety of the pyridine cycle alongside radical and charged oxygen centers of the imidazoline fragment. Notably, the introduction of fluorine atoms diminished the antiarrhythmic effect, while the most potent derivatives featured the nitronyl nitroxide pattern positioned at the third site of the pyridine cycle. Gender-dependent responses were observed in lead compounds LCF3 and LMe, with LMe inducing temporary bradycardia and hypotension specifically in female rats, and LCF3 causing significant blood pressure reduction followed by rebound in females compared to milder effects in males. Mechanistic insights point towards β1 adrenoceptor blockade as an underlying mechanism, supported by experiments on isolated rat atria. This research underscores the interplay between structure, cardiovascular effects and gender-specific responses, offering insights for therapeutic strategies for treating free radical-associated cardiovascular disorders.

Late Sodium Current Inhibitors as Potential Antiarrhythmic Agents.

Based on recent findings, an increased late sodium current (INa,late) plays an important pathophysiological role in cardiac diseases, including rhythm disorders. The article first describes what is INa,late and how it functions under physiological circumstances. Next, it shows the wide range of cellular mechanisms that can contribute to an increased INa,late in heart diseases, and also discusses how the upregulated INa,late can play a role in the generation of cardiac arrhythmias. The last part of the article is about INa,late inhibiting drugs as potential antiarrhythmic agents, based on experimental and preclinical data as well as in the light of clinical trials.

Antiarrhythmic Effects of Chronic Melatonin Treatment Are Not Associated with Its Antioxidative Action in Rat Myocardial Ischemia/Reperfusion Model

IntroductionMelatonin was proposed as a potential antiarrhythmic agent, and its antioxidative properties are considered to be the basis for the antiarrhythmic effect. The present study was aimed at the evaluation of association between ventricular tachycardia and/or ventricular fibrillation (VT/VF) incidence, oxidative stress parameters and electrophysiological changes in myocardial ischemia/reperfusion setting.Methods18 rats were treated by melatonin (10 mg/kg/day, orally) for 7 days, while 13 control animals were given placebo. The left anterior descending artery was reversibly ligated for 5 min to induce ischemia and subsequent reperfusion in the anesthetized animals. Unipolar electrograms were recorded from ventricular epicardium with a 64‐lead array connected to a custom‐made high‐resolution (4 kHz) mapping system. Local activation and repolarization times were measured as instants of dV/dt min during QRS complexes and dV/dt max during T waves in unipolar electrograms, respectively. Local repolarization durations and dispersion of repolarization were calculated. After experiments, the hearts were excised, and parameters of the oxidative stress were determined in ventricular myocardium.ResultsVT/VF incidence was less in the animals given melatonin as compared to controls (6/18 vs 9/13, p=0.047, respectively). Superoxide dismutase activity was higher in the melatonin group as compared to the control group (69.6±0.5 vs 60.2±2.0 inhibition rate %, p=0.001, respectively), while total antioxidant capacity, 4‐HNE adduct and total glutathione content did not differ in the studied groups. No parameters of oxidative stress were associated with arrhythmia susceptibility. Among the studied ventricular epicardial electrophysiological parameters, local activation times at the baseline (preischemic) state were both reduced by melatonin treatment (9.39±0.26 vs 10.58±0.33 ms, p=0.012) and associated with VT/VF incidence (B=1.872, 95% CI 1.106–3.169, p=0.020) in logistic regression analysis. No association between parameters of ventricular electrical excitation and oxidative stress were found.ConclusionThough chronic melatonin treatment enhanced enzymatic antioxidant activity, its antiarrhythmic action in ischemia/reperfusion model was associated with its direct effect on ventricular activation pattern.Support or Funding InformationThe study was supported by Russian Science Foundation (RSF 18‐15‐00309).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Allicin disrupts cardiac Cav1.2 channels via trafficking

Context: Allicin is a potential antiarrhythmic agent. The antiarrhythmic properties of allicin rely on its blockade of various cardiac ion channels. The l-type calcium (Cav1.2) channel provides a pivotal substrate for cardiac electrophysiologic activities. The mechanism of allicin on Cav1.2 remains unclear.Objective: This study evaluated the potential of allicin on the synthesis and trafficking of Cav1.2 channels.Materials and methods: Primary cardiomyocytes (CMs) from neonatal Sprague-Dawley (SD) rats were exposed to allicin (0, 0.0001, 0.001, 0.01, 0.1, 1, 10, 100 μg/mL) for 24 and 48 h. The CellTiter-Glo assay was performed to measure CM viability. Western blot with grayscale analysis and confocal laser scanning microscopy were used to evaluate the effects of allicin on the synthesis and trafficking of Cav1.2 channel proteins in primary CMs.Results: There was no significant difference in apoptotic toxicity from the actual cell viability (p > 0.05) in any group (0, 0.0001, 0.001, 0.01, 0.1, 1, 10, 100 μg/mL allicin), except that viability in the 0.001 and 0.01 μg/mL groups at 24 h were significantly greater (137.37 and 135.96%) (p < 0.05). Western blot with grayscale analysis revealed no substantial inhibition by allicin of the synthesis of Cav1.2 proteins. Confocal laser scanning microscopy revealed trafficking dysfunction of Cav1.2 channels caused by allicin in primary CMs.Conclusion: This study is the first to demonstrate that allicin inhibits cardiac Cav1.2 channels by disrupting trafficking, possibly mediating its antiarrhythmic benefits. Therefore, allicin might serve as a new antiarrhythmic agent in the future.

Computer Simulations Reveal a Novel Blocking Mode of the hERG Ion Channel by the Antiarrhythmic Agent Clofilium.

The binding modes of many hERG ion channel blockers are well understood, but a notable exception is clofilium, a potent antiarrhythmic agent whose action relies on blocking the current mediated by hERG. From the previously hypothesized binding modes of clofilium to hERG, only two can explain most of the experimental results. In this study, computer simulations are performed in order to analyze the hypothesized binding modes and to identify the consensus one. This is accomplished by employing molecular dynamics (MD) simulations and interaction energy calculations. The results show an unexpected binding mode, in which the quaternary nitrogen is placed in the upper part of the inner cavity, interacting strongly with Ser624, while the chlorophenyl group is located in the lower part, in better agreement with previous experimental results. This novel binding position also explains the higher affinity of clofilium for the related hEag1 channel and was correlated with the possibility that potent hERG blockers interact in specific ways with the residues near the intracellular activation gate, offering a new explanation that could help predict the potency of other hERG-blocking compounds.

Effects of diacetyl-liensinine on electrophysiology in rabbit ventricular myocytes

BackgroundDiacetyl-liensinine is a chemosynthetic derivative of liensinine, extracted from the seed embryo of Nelumbo nucifera Gaertn, in China. It has been found to have extensive anti- arrhythmic actions. The present study was designed to investigate the effects of diacetyl-liensinine on electro- physiology of myocytes.MethodsWe exposed rabbit ventricular myocytes to diacetyl-liensinine using standard whole-cell patch-clamp technique and measured the action potential, L-type calcium current (ICa-L), delayed rectifier potassium current (IK), transient outward potassium current (Ito) and inward rectifier potassium current (IK1).ResultsOur results showed that diacetyl-liensinine significantly prolonged action potential duration at 50 and 90% repolarization (APD50, APD90), at 10 and 30 μM, while shortened APD50 and APD90 at 100 μM. In addition, diacetyl-liensinine inhibited the ICa-L, IK, Ito and IK1 in a concentration-dependent manner.ConclusionsThe results suggest that diacetyl-liensinine might be a potential anti-arrhythmic agent.

Different electrophysiological effects of the levo- and dextro-rotatory isomers of mexiletine in isolated rabbit cardiac muscle.

Racemic mexiletine is a widely used antiarrhythmic agent that blocks sodium channels. The effects of R-(-) and S-(+) mexiletine stereoisomers on maximum rate of depolarization ([Formula: see text]), conduction time, and repolarization have not yet been investigated in isolated cardiac preparations. We studied the effect of the R-(-) and S-(+) mexiletine on rabbit cardiac action potential parameters by using the conventional microelectrode technique. Both enantiomers at 20 μmol/L of therapeutically and experimentally relevant concentration, significantly depressed the [Formula: see text] at fast heart rates (BCLs 300-700 ms). R-(-) mexiletine has more potent inhibitory effect than S-(+) mexiletine. Both R-(-) and S-(+) mexiletine significantly inhibited the [Formula: see text] of early extrasystoles measured at 70 ms diastolic interval induced by S1-S2 stimuli. R-(-) mexiletine has more pronounced inhibitory effect than S-(+) mexiletine. Both R-(-) and S-(+) mexiletine increased significantly the ERP/APD90 ratio. The time constant (τ) of recovery of [Formula: see text] was found to be τ = 376.0 ± 77.8 ms for R-(-) mexiletine and τ = 227.1 ± 23.4 ms for S-(+) mexiletine, which indicates a slower offset kinetics for R-(-) mexiletine from sodium channels than that of the S-(+) enantiomer. These data suggest that R-(-) mexiletine might be a more potent antiarrhythmic agent than S-(+) mexiletine.

Total Thyroidectomy for Amiodarone-induced Thyrotoxicosis in the Hyperthyroid State

Amiodarone is a potent antiarrhythmic agent, indicated for the treatment of refractory arrhythmias, which may lead to thyrotoxicosis. In these patients, thyroidectomy is a valid therapeutic option. Antithyroid therapy in the immediate preoperative setting and the subsequently accepted minimal delay until thyroidectomy have not been clearly defined yet. The aim of the present study was to show, that total thyroidectomy under general anaesthesia in patients with amiodarone-induced thyrotoxicosis (AIT) is safe without necessarily obtaining an euthyroid state preoperatively.We conducted a retrospective cohort study of prospectively gathered data on 11 patients undergoing total thyroidectomy under general anaesthesia between January 2008 and December 2013 for AIT at our University Hospital.All patients were preoperatively treated with carbimazole, steroids and β-receptor antagonists. Additionally, 3 patients received potassium perchlorate and in one patient carbimazole was changed to propylthiouracil. Plasmapheresis was performed in 3 patients. Only one patient was euthyroid at the time of operation. There were no significant intra- and postoperative complications, especially no signs of thyroid storm. One patient could postoperatively be removed from the cardiac transplant waiting list due to improved cardiac function.Improvements in the interdisciplinary surgical management for AIT between cardiologists, endocrinologists, anaesthetists and endocrine surgeons provide the basis of safe total thyroidectomy under general anaesthesia in hyperthyroid state. Early surgery without long delay for medical antithyroid treatment (with its potential negative side effects) is recommended.

Антиаритмическая активность n-ацетильного производного l-глутаминовой кислоты при острой ишемии миокарда и стрептозотоциновом сахарном диабете

Anti-arrhythmic activity of liquid dosage forms of N-acetyl-L-glutamic acid internally introduced was studied in experiments on animals with streptozotocin diabetes mellitus and acute myocardial ischemia. The prescription of this compound to rats with diabetes in the dose of 125 mg/kg / day for 14 days and it use prevents early occlusion and reperfusion arrhythmias, resulting in a statistically significant reduction in the development of ventricular arrhythmias and ventricular fibrillation. The studies in dogs with diabetes mellitus proved that prophylactic introduction N-acetyl-L-glutamic acid at a dose of 60 mg/kg is accompanied by full and partial suppression of ectopic activity on the second day after the formation of acute myocardial infarction, reduction of metabolic acidosis and increased oxygen consumption in the ischemic zone of alteration. The results suggest that the course introduction domestic derivative of L-glutamic acid in animals of different species prevents the formation of ischemia-mediated cardiovascular events and can be as potential anti-arrhythmic agent. The work is supported by the project (project code-2859) performed by Mordovia State N.P. Ogarev University and RFBR grant 14-04-31104.

Recurrent Torsades de Pointes Due to Amiodarone Toxicity Treated Successfully with Lidocaine.

The Editor, Sir, Amiodarone is a potent antiarrhythmic agent that is used to treat ventricular arrhythmias and atrial fibrillation. Proarrythmias due to amiodarone therapy is rare. We discuss a case who had amiodarone-induced incessant Torsades de Pointes (TdP), that could only be suppressed by lidocaine.

Kinetic Model for NS1643 Drug Activation of WT and L529I Variants of Kv11.1 (hERG1) Potassium Channel

Congenital and acquired (drug-induced) forms of the human long-QT syndrome are associated with alterations in Kv11.1 (hERG) channel-controlled repolarizing IKr currents of cardiac action potentials. A mandatory drug screen implemented by many countries led to a discovery of a large group of small molecules that can activate hERG currents and thus may act as potent antiarrhythmic agents. Despite significant progress in identification of channel activators, little is known about their mechanism of action. A combination of electrophysiological studies with molecular and kinetic modeling was used to examine the mechanism of a model activator (NS1643) action on the hERG channel and its L529I mutant. The L529I mutant has gating dynamics similar to that of wild-type while its response to application of NS1643 is markedly different. We propose a mechanism compatible with experiments in which the model activator binds to the closed (C3) and open states (O). We suggest that NS1643 is affecting early gating transitions, probably during movements of the voltage sensor that precede the opening of the activation gate.

Role of Fructose as a Potent Antiarrhythmic and Anti-infarct agent in Isolated Rat Heart.

In the current study, effects of acute short term administration of fructose on cardiac arrhythmias and myocardial infarction size following ischemia/reperfusion were investigated in isolated rat heart. The hearts were subjected to 30 min zero flow global ischemia followed by 120 min reperfusion. In the control group, the hearts were perfused by normal drug free Krebs-Henseleit (K/H) solution throughout the experiments, while in the treated groups (2-4), they were perfused with fructose containing K/H solution at 12, 24 and 48 mM concentrations during stabilization and reperfusion time, respectively. Cardiac arrhythmias were determined based on the Lambeth conventions and the infarct size was measured by computerized planimetry. Myocardial infarction size was 22 ± 3% in the control group, however administration of fructose (12, 24 and 48 mM) reduced it to 15 ± 3 (P<0.05), 7±2 (P<0.001) and 4 ± 2% (P<0.001), respectively. A direct linear correlation between fructose concentrations and infarction size reduction was observed (R(2)=0.970). In addition, total number of ventricular ectopic beats were significantly decreased by all used concentrations of fructose (P<0.01 for group 2, P<0.001 for groups 3 and 4, respectively). Fructose also produced significant decrease in the number, incidence and duration of ventricular tachycardia compared to the control (P<0.05). The data showed that acute short term administration of fructose can protect isolated rat heart against ischemia/reperfusion injuries as reduction of infarct size and cardiac arrhythmias. Alterations in glycogen storage and/or glycolytic efficiency may probably involve in these cardioprotective effects. Also it is possible that fructose can act as a pharmacological preconditioning agent.

Protective effects of saffron (Crocus sativus) against lethal ventricular arrhythmias induced by heart reperfusion in rat: A potential anti-arrhythmic agent

Context: Saffron (Crocus sativus L.) has been used as a cuisine spice in eastern and western societies for thousands of years. In traditional medicine, saffron is recommended for the treatment of various kinds of disorders including heart palpitations.Objective: We investigated the hypothesis of the protective effect of saffron on lethal cardiac arrhythmias induced by heart ischemia-reperfusion in rat.Materials and methods: Animals were divided into a control (CTL) group that received tap water, Saf50, Saf100 and Saf200 groups that were orally treated with aqueous extracts of saffron, at dosages of 50, 100 and 200 mg/kg/day, respectively, and amiodarone (Amio) group that orally received 30 mg/kg/day for seven days. On day 8, heart ischemia-reperfusion was induced by ligation and releasing of the left anterior descending coronary artery.Results: During reperfusion, the numbers and durations of ventricular fibrillation (VF) decreased in all groups compared to the CTL group (p < 0.05). Ventricular tachycardia (VT)/VF numbers (3.2 ± 1.2), durations (4.9 ± 2.6) and also arrhythmia severity (1.9 ± 0.35) were decreased significantly in the Saf100 group versus CTL group values (18.4 ± 11.6, 52 ± 31 and 3.3 ± 0.3, respectively). The PR and QTcn intervals of ECG were significantly longer in the Saf200 group (p < 0.001 versus CTL). The other doses of saffron only significantly prolonged the QTcn interval.Conclusion: The results suggest that pretreatment with saffron, especially at the dosage of 100 mg/kg/day, attenuates the susceptibility and incidence of fatal ventricular arrhythmia during the reperfusion period in the rat. This protective effect is apparently mediated through reduction of electrical conductivity and prolonging the action potential duration.

Semisynthesis and Myocardial Activity of Thaliporphine N-Homologues

The N-homologues and optical isomers of thaliporphine (5a), a potent antiarrhythmic agent, were prepared starting from laurolitsine (1), an abundant aporphine present in Phoebe formosana. Treating N-propylnorglaucine with 90% H2SO4 yielded one additional product, an 11-sulfonyl-1,11-anhydroaporphine. Reaction of N-formylnorglaucine (3a) with 90% H2SO4, however, yielded the 9-sulfonyl-seco product as a major product. Treatment of 3a with 98% H2SO4 yielded pancordine (10), which, upon catalytic hydrogenation, yielded (±)-wilsonirine. (1)H NMR spectroscopic analysis was applied successfully to monitor the optical purity of the crystalline salt while undertaking optical resolution. Thaliporphine (5a) was demonstrated to possess better positive inotropic and less negative chronotropic effects than the left-hand optical isomer and showed the best activity on rat cardiac tissue among the N-homologues prepared.

Arctigenin, a Potential Anti-Arrhythmic Agent, Inhibits Aconitine-Induced Arrhythmia by Regulating Multi-Ion Channels

Background/Aims: Arctigenin possesses biological activities, but its underlying mechanisms at the cellular and ion channel levels are not completely understood. Therefore, the present study was designed to identify the anti-arrhythmia effect of arctigenin in vivo, as well as its cellular targets and mechanisms. Methods: A rat arrhythmia model was established via continuous aconitine infusion, and the onset times of ventricular premature contraction, ventricular tachycardia and death were recorded. The Action Potential Duration (APD), sodium current (I_Na), L-type calcium current (I_{Ca, L}) and transient outward potassium current (I_to) were measured and analysed using a patch-clamp recording technique in normal rat cardiomyocytes and myocytes of arrhythmia aconitine-induced by. Results: Arctigenin significantly delayed the arrhythmia onset in the aconitine-induced rat model. The 50% and 90% repolarisations (APD₅₀ and APD₉₀) were shortened by 100 µM arctigenin; the arctigenin dose also inhibited the prolongation of APD₅₀ and APD₉₀ caused by 1 µM aconitine. Arctigenin inhibited I_Na and I_Ca,L and attenuated the aconitine-increased I_Na and I_Ca,L by accelerating the activation process and delaying the inactivation process. Arctigenin enhanced I_to by facilitating the activation process and delaying the inactivation process, and recoverd the decreased I_to induced by aconitine. Conclusions: Arctigenin has displayed anti-arrhythmia effects, both in vivo and in vitro. In the context of electrophysiology, I_Na, I_{Ca, L}, and I_to may be multiple targets of arctigenin, leading to its antiarrhythmic effect.

Update on the Slow Delayed Rectifier Potassium Current (IKs): Role in Modulating Cardiac Function

The slow delayed rectifier current (I(Ks)) is the slow component of cardiac delayed rectifier current and is critical for the late phase repolarization of cardiac action potential. This current is also an important target for Sympathetic Nervous System (SNS) to regulate the cardiac electivity to accommodate to heart rate alterations in response to exercise or emotional stress and can be up-regulated by β- adrenergic or other signal molecules. I(Ks) channel is originated by the co-assembly of pore-forming KCNQ1 α-subunit and accessory KCNE1 β-subunit. Mutations in any subunit can bring about severe long QT syndrome (LQT-1, LQT-5) as characterized by deliquium, seizures and sudden death. This review summarizes the normal physiological functions and molecular basis of I(Ks) channels, as well as illustrates up-to-date development on its blockers and activators. Therefore, the current extensive survey should generate fundamental understanding of the role of I(Ks) channel in modulating cardiac function and donate some instructions to the progression of I(Ks) blockers and activators as potential antiarrhythmic agents or pharmacological tools to determine the physiological and pathological function of I(Ks).

Antiarrhythmic properties of phenylpiperazine derivatives of phenytoin with α1-adrenoceptor affinities

An association between α1-adrenoceptor affinities, hERG K+-antagonistic properties and antiarrhythmic activities for a series of phenylpiperazine derivatives of hydantoin (2a–21a) was investigated. New compounds were synthesized and tested for their affinity for α1-adrenoceptors in radioligand binding assay using [3H]-prazosin as a selective radioligand. Antiarrhythmic activities in adrenaline- and barium chloride-induced arrhythmia models, an influence of the phenylpiperazine derivatives on the ECG-components and blood pressure were tested in vivo in normotensive rats. The hERG K+-antagonistic properties of the most potent antiarrhythmic agents were investigated in silico by the use of program QikProp. The highest α1-adrenoceptor affinity (Ki=4.7nM) and the strongest antiarrhythmic activity in adrenaline induced arrhythmia (ED50=0.1mg/kg) was found for 1-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione hydrochloride (19a). The results indicated a significant correlation between α1-AR affinities (pKi) and antiarrhythmic activity (ED50) in adrenaline model (R2=0.92, p <0.005). Influence of the examined phenylpiperazine hydantoin derivatives on hERG K+ channel, predicted by means of in silico methods, suggested their hERG K+-blocking properties.

Synthesis and preliminary biological evaluation of novel N-substituted 1-amino-3-[1-methyl(phenyl)-1H-indazol-4-yloxy]-propan-2-ols interesting as potential antiarrhythmic, local anaesthetic and analgesic agents.

A series of indazoloxypropanolamines 7 and 8, pindolol isosteres, were synthesized to extend the structure activity relationship (SAR) which was observed in an earlier series of related derivatives. Compounds 7, characterized by methyl substitution on the N-1 indazole nucleus, generally exhibited significant antiarrhythmic, local anaesthetic and analgesic activities. The preliminary radioligand binding assay highlighted, in compounds 7, an interesting beta 1-affinity which can be well correlated to their antiarrhyhtmic activity. Analogues 8 characterized by a phenyl group on the N-1 indazole nucleus, were generally less active as antiarrhyhtmic agents but generally interesting as local anaesthetics. Due to the importance of the indazole moiety as a carrier of antiphlogistic activity, the two classes of derivatives 7 and 8 were evaluated for their NSAID behaviour. Once again, compounds 7 resulted having more interesting analgesic and antipyretic effects than analogues 8.

Electrophysiological mechanisms of sophocarpine as a potential antiarrhythmic agent

To examine the electrophysiological effects of sophocarpine on action potentials (AP) and ionic currents of cardiac myocytes and to compare some of these effects with those of amiodarone. Langendorff perfusion set-up was used in isolated guinea pig heart, and responses to sophocarpine were monitored using electrocardiograph. Conventional microelectrode, voltage clamp technique and perforated patch were employed to record fast response AP (fAP), slow response AP (sAP) and ionic currents in guinea pig papillary muscle or rabbit sinus node cells. Tachyarrhythmia produced by isoprenaline (15 μmol/L) could be reversed by sophocarpine (300 μmol/L). Sophocarpine (10 μmol/L) decreased the amplitude by 4.0%, maximal depolarization velocity (V(max)) of the fAP by 24.4%, and Na(+) current (I(Na)) by 18.0%, while it prolonged the effective refractory period (ERP) by 21.1%. The same concentration of sophocarpine could also decrease the amplitude and V(max) of the sAP, by 26.8% and 25.7%, respectively, and attenuated the Ca(2+) current (I(CaL)) and the K(+) tail current substantially. Comparison of sophocarpine with amiodarone demonstrated that both prolonged the duration and the ERP of fAP and sAP, both decreased the amplitude and V(max) of the fAP and sAP, and both slowed the automatic heart rate. Sophocarpine could reverse isoprenaline-induced arrhythmia and inhibit I(Na), I(CaL), and I(Kr) currents. The electrophysiological effects of sophocarpine are similar to those of amiodarone, which might be regarded as a prospective antiarrhythmic agent.