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Hepatitis B virus (HBV) belongs to Hepadnaviridae family and mainly infects hepatocytes, which can cause acute or chronic hepatitis. Currently, two types of antiviral drugs are approved for chronic infection clinically: interferons and nucleos(t)ide analogues. However, the clinical cure for chronic infection is still rare, and it is a huge challenge for all researchers to develop high-efficiency, safe, non-tolerant, and low-toxicity anti-HBV drugs. Antazoline hydrochloride is a first-generation antihistamine with anticholinergic properties, and it is commonly used to relieve nasal congestion and in eye drops. Recently, an in vitro high-throughput evaluation system was constructed to screen nearly 800 compounds from the Food and Drug Administration (FDA)-approved Drug Library. We found that arbidol hydrochloride and antazoline hydrochloride can effectively reduce HBV DNA in the extracellular supernatant in a dose-dependent manner, with EC(50) of 4.321 μmol/L and 2.910 μmol/L in HepAD38 cells, respectively. Moreover, the antiviral effects and potential mechanism of action of antazoline hydrochloride were studied in different HBV replication systems. The results indicate that antazoline hydrochloride also has a significant inhibitory effect on HBV DNA in the extracellular supernatant of Huh7 cells, with an EC(50) of 2.349 μmol/L. These findings provide new ideas for screening and research related to HBV agents.

Antazoline is an antihistaminic, immunosuppressive, antiarrhythmic agent. Antazoline can be administered orally, intravenously, intramuscularly or via the ophthalmic route. Antazoline has a limited application as an antiarrhythmic drug. This review was undertaken with the aim to combine the old and the new results of different types of studies (clinical, retrospective, or pharmacokinetic) and sum up the positive and negative effects of antazoline in cardiology and emergency medicine. A literature queries were performed in the following databases: PubMed, Embase, Google Scholar, and Web of Science (all from their inception date till June 2019). The queries covered antazoline in combinations with such terms as antiarrhythmic activity, arrhythmia, electrocardiography, emergency medicine, and cardiology. Additional publications were found by checking all the reference lists. The newest research shows that antazoline may have the highest success rate of pharmacological cardioversion among all drugs used in the contemporary treatment of cardiac arrhythmia (up to 85.3%). The rate of cardioversion with antazoline alone was higher than the combined amiodarone and/or propafenone. Most of the studies which were reviewed indicated that paroxysmal atrial fibrillation, compared to chronic atrial fibrillation, responded more satisfactorily to antazoline treatment. Most patients tolerated antazoline well and conversion was safe, effective, and smooth. Some research proves that antazoline use may also reduce the rate of hospitalization due to the adverse effects. Antazoline has a definite place in the therapeutic repertoire for several cardiac arrhythmias. It should not be neglected as an old drug, and ought to be reconsidered in emergency medicine treatment recommendations.

Pharmacological cardioversion (PCV) is commonly a primary option for termination of recent-onset atrial fibrillation (AF) in emergency departments (ED). This is a subanalysis of the CANT II study, evaluating the effectiveness and safety of antazoline in patients (n = 777) at three stages of chronic kidney disease (CKD): Group I > 60 mL/min (n = 531), Group II 45–59 mL/min (n = 149), and Group III < 45 mL/min (n = 97). Patients in Group III were older and with a higher prevalence of co-morbidities; however, we did not find statistically significant differences in the overall effectiveness of PCV in comparison with the other groups. In patients receiving amiodarone, the PCV success rate was similar in all the studied groups, but along with a renal function decline, it decreased in patients receiving antazoline (79.1 vs. 35%; p < 0.001), and it increased almost significantly in patients receiving propafenone (69.9 vs. 100%; p = 0.067). In patients in Group I, antazoline restored a sinus rhythm as effectively as propafenone and amiodarone; however, in patients in Group III, both antazoline and amiodarone became less effective in restoring a sinus rhythm than propafenone (p = 0.002 and p = 0.034, respectively). The rate of safety endpoint was the highest in patients in Group III (eGFR < 45 mL/min), and it was significantly higher than in patients in Groups I and II (p = 0.008 and p = 0.036, respectively). We did not observe antazoline-related adverse events in any of the studied groups of patients. This real-world registry analysis revealed a different influence of CKD on the effectiveness of individual drugs, and while propafenone and amiodarone maintained their AF termination efficacy, antazoline became significantly less effective in restoring sinus rhythm.

Due to safety concerns about available antiarrhythmic drugs (AADs), reliable agents for termination of atrial fibrillation (AF) are requisite.The aim of the study was to evaluate the efficacy and safety of antazoline, a first‑generation antihistamine, for cardioversion of recent‑onset AF in the setting of an emergency department.This multicenter, retrospective registry covered 1365 patients (median [interquartile range] age, 69.0 [61.0-76.0] years, 53.1% men) with new‑onset AF submitted to urgent pharmacological cardioversion. AAD allocation was performed by the attending physician: antazoline alone was utilized in 600 patients (44%), amiodarone in 287 (21%), propafenone in 150 (11%), and ≥2 AADs in 328 patients (24%). Antazoline in monotherapy or combination was administered to 897 patients (65.7%). Matched antazoline and nonantazoline groups were identified using propensity score matching (PSM, n = 330). The primary end point was return to sinus rhythm within 12 hours after initiation of the treatment.Before PSM, antazoline alone was superior to amiodarone (78.3% vs 66.9%; relative risk [RR], 1.17; 95% CI, 1.07-1.28; P0.001) and comparable to propafenone (78.3% vs 72.7%; RR, 1.08; 95% CI, 0.97-1.20; P = 0.14) in terms of rhythm conversion rate. In the post‑PSM population, the rhythm conversion rate was higher among patients receiving antazoline alone than in the nonantazoline group (84.2% vs 66.7%; RR, 1.26; 95% CI, 1.11-1.43; P0.001), and the risk of adverse events was comparable (P = 0.2).Antazoline appears to be an efficacious agent for termination of AF in real‑world setting. Randomized controlled trials are required to evaluate its safety in specific patient populations.

INTRODUCTION Little is known about the safety and effectiveness of pharmacological cardioversion of recent-onset atrial fibrillation (AF) in the elderly. Antazoline has already been shown to be effective and safe in a wide variety of patients. OBJECTIVES To compare clinical effectiveness and safety of iv antazoline administered for pharmacological cardioversion of recent-onset AF in patients aged ≥75 years and younger. PATIENTS AND METHODS This retrospective analysis was conducted using data derived from emergency room medical records of patients qualified for pharmacological cardioversion due to symptomatic AF lasting less than 48 hours. For the purpose of the analysis the threshold for old age was set at 75 years. Conversion to sinus was considered a primary effectiveness outcome. The primary safety outcome was defined as any adverse event (AE) leading to hospitalization. RESULTS Out of 334 patients, 110 patients ≥75 years old comprised the study group. Successful CV was achieved using smaller doses of antazoline in the study group than in the control group: 151 (59) mg vs. 168 (58) mg (P = 0.039). The effectiveness and safety of antazoline was similar in patients aged ≥75 and

Introduction Antazoline (ANT) is an old antihistaminic medication with antiarrhythmic properties. After intravenous administration ANT exerts rapid antiarrhythmic effect often resulting in conversion of atrial fibrillation (AF) to sinus rhythm (SR) and is widely used in Poland for this purpose in the last years. However, published data on its effectiveness, safety and clinical utility for rapid AF termination are limited and ANT is not recognized as a cardioversion drug. Aim To assess the real-world efficacy of ANT for pharmacological cardioversion of paroxysmal and persistent non-valvular AF. Methods Our single center, retrospective, observational study included patients (pts) with history paroxysmal or persistent AF episode lasting less than 6 months, in stable cardiopulmonary condition who were qualified for elective pharmacological cardioversion with intravenous ANT. The primary end-point was the conversion of AF to SR confirmed in electrocardiography (ECG) during the 6-hours observation. Results A total of 176 pts (mean age 68.4±12.0 years, 49% male) were enrolled into the study. In 93 patients (52%) AF duration was shorter than 48 hours and median AF duration time was 24 (7–432) hours. The overall success rate of pharmacological cardioversion of AF with intravenous ANT was 45.5% (80/176 pts). The mean used dose of ANT was 250.9±65.4mg. The subgroup analysis, regarding the AF duration, suggested the effectiveness of ANT mainly in in short-lasting AF (effectiveness of antazoline based cardioversion for AF lasting Conclusions Antazoline is effective and safe in rapid pharmacological cardioversion of paroxysmal AF, especially in the short-lasting AF ( Funding Acknowledgement Type of funding sources: None. Figure 1. ROC curve analysis

Aims Antazoline is a first-generation antihistaminic drug used primarily in eye drop formulations. When administered intravenously, antazoline displays antiarrhythmic properties resulting in a rapid conversion of recent-onset atrial fibrillation (AF) to sinus rhythm (SR). The aim of the study was to assess the influence of antazoline on atrio-venous conduction and other electrophysiological parameters in patients undergoing AF ablation. Methods An experimental prospective study. Patients scheduled for the first-time AF ablation, in SR and not on amiodarone were enrolled. Atrio-venous conduction assessment and invasive electrophysiological study (EPS) were performed before and after intravenous administration of 250 mg of antazoline. In case of AF induction during EPS, antazoline was administered until conversion to SR or a cumulative dose of 300 mg. Results We enrolled 14 patients: 13 (93%) men, mean age 63.4 (59.9-66.8) years, mean CHA2 DS2 -VASc score 1.6 (1.0-2.2). Antazoline was administered in a mean dose 257.1 (246.7-267.6) mg. Pulmonary vein potentials and atrial capture during pulmonary vein stimulation were present before and after the administration of antazoline. Wenckebach point and atrial conduction times did not change significantly, but atrio-ventricular node effective refractory period improved-324.7 (275.9-373.5) ms vs 284.3 (256.2-312.4) ms, P = 0.02. Antazoline was effective in all 5 (100%) cases of AF induction during EPS. There were no serious adverse events. Conclusion Due to the lack of influence on atrio-venous conduction and high clinical effectiveness, antazoline may be suitable for pharmacological cardioversion of AF occurring during AF ablation.

Funding Acknowledgements Type of funding sources: None. Introduction Antazoline (ANT) is an old antihistaminic medication with antiarrhythmic properties. After intravenous administration ANT exerts rapid antiarrhythmic effect often resulting in conversion of persistent atrial fibrillation (AF) to sinus rhythm (SR). However, published data on its effectiveness, safety and clinical utility for rapid AF termination are limited and ANT is not recognized as a cardioversion drug. Aim To assess the real-world efficacy of ANT for pharmacological cardioversion of paroxysmal and persistent non-valvular AF. Methods We conducted a single center, retrospective, observational study including patients (pts) with history paroxysmal or persistent AF episode lasting less than 6 months, in stable cardiopulmonary condition who were qualified for elective pharmacological cardioversion with intravenous ANT. The primary end-point was the conversion of AF to SR confirmed in electrocardiography (ECG) during the 6-hours observation. Results A total of 176 pts (mean age 68.4 ± 12.0 years, 49% male) were enrolled into the study. In 93 patients (52%) AF duration was shorter than 48 hours and median AF duration time was 24 (7 – 432) hours. The overall success rate of pharmacological cardioversion of AF with intravenous ANT was 45.5% (80/176 pts). The mean used dose of ANT was 250.9 ± 65.4mg. The subgroup analysis, regarding the AF duration, suggested the effectiveness of ANT mainly in in short-lasting AF (effectiveness of antazoline based cardioversion for AF lasting Conclusions Intravenous antazoline administration is effective and safe in rapid pharmacological cardioversion of paroxysmal AF, especially in the short-lasting AF (

Background Antazoline mesylate represents a first generation antihistamine with quinidine-like antiarrhythmic properties, which allows for rapid and effective termination of atrial fibrillation (AF). Despite its widespread use in Polish emergency departments, paucity of data exists concerning safety and efficacy of antazoline in comparison to other antiarrhythmic agents. Purpose This study aimed to evaluate the pooled hitherto data on effectiveness and safety of pharmacological Cardioversion with intravenous ANTazoline (CANT Study) in short-duration atrial fibrillation. Methods This retrospective observational study was performed in 5 medical centers and comprised 1300 patients with paroxysmal or persistent AF who underwent emergent pharmacological cardioversion in the real-world setting of emergency or cardiology department. The choice of antiarrhythmic drug was left to the discretion of attending physician. The exclusion criteria involved permanent AF, other supraventricular arrhythmias, including atrial flutter, chronic antiarrhythmic therapy or preemptive electrical cardioversion. The primary endpoint was restoration of sinus rhythm up to 12 hours after antiarrhythmic drug infusion. The combined safety endpoint was bradycardia Results The mean age of study population was 67.7±11.6 years and the majority of patients were men (52.9%). The median AF episode duration was 10 (4; 24) hours, while median CHA2DS2-VASc score was 3 (2; 4) pts. Antazoline alone was administered in 45.6% of patients (n=593); amiodarone in 22.1% (n=287); propafenone in 11.5% (n=150); sotalol in 0.5% (n=6), while 20.3% (n=264) received overlapping antiarrhythmic therapy. Antazoline had the highest rhythm conversion rate (Figure), which was comparable to propafenone (78.2% vs 72.7%; RR 1.08; 95% CI:0.97–1.20; P=0.175) and superior to amiodarone (vs 66.9%; RR 1.17, 95% CI:1.07–1.28; P=0.0008) and collective amiodarone/propafenone/sotalol treatment (vs 68.6%; RR 1.14; 95% CI:1.06–1.23; P=0.0006). The rate of combined safety endpoint was comparable in patients treated with antazoline and other antiarrhythmic drugs (5.2% vs 3.9%; P=0.297). Among patients treated with antazoline, 29 exhibited bradycardia Conclusion Antazoline appears to be an effective antiarrhythmic drug for cardioversion of atrial fibrillation, which is associated with low rate of relatively benign adverse events. Figure 1 Funding Acknowledgement Type of funding source: None

Antazoline (ANT) was recently shown to be an effective and safe antiarrhythmic drug in the termination of atrial fibrillation. However, the drug is still not listed in clinical guidelines. No data on ANT metabolism in humans is available. We used liquid chromatography coupled with tandem mass spectrometry to identify and characterize metabolites of ANT. We analyzed plasma of volunteers following a single intravenous administration of 100 mg of ANT mesylate and in in vitro cultures of human hepatocytes. We revealed that ANT was transformed into at least 15 metabolites and we investigated the role of cytochrome P450 isoforms. CYP2D6 was the main one involved in the fast metabolism of ANT. The biotransformation of ANT by CYP2C19 was much slower. The main Phase I metabolite was M1 formed by the removal of phenyl and metabolite M2 with hydroxyl in the para position of phenyl. Glucuronidation was the leading Phase II metabolism. Further study on pharmacokinetics of the metabolites would allow us to better understand the activity profile of ANT and to predict its potential clinical applications. Ultimately, further investigation of the activity profile of the new hydroxylated M2 metabolite of ANT might result in an active substance with a different pharmacological profile than the parent molecule, and potentially a new drug candidate.

Background Former studies corroborated promising quinidine-like properties of antazoline mesylate facilitating rapid cardioversion atrial fibrillation (AF). Still, paucity of data exists concerning direct comparison of antazoline to other antiarrhythmic agents. Purpose The study aimed to verify the hypothesis that intravenous antazoline is non-inferior to amiodarone and/or propafenone in terms of rhythm conversion rate and safety among patients with AF. Methods After reviewing 2344 consecutive medical records with I48 code of international classification of diseases (ICD), 505 eligible patients (21.5%) with paroxysmal or persistent AF who underwent emergent pharmacological cardioversion in the real-world setting of emergency department were enrolled in retrospective observational analysis. The choice of antiarrhythmic drug was left to the discretion of attending physician. Antazoline group was separately matched with corresponding amiodarone (n=218) and propafenone (n=90) cohort using propensity score matching (PSM) with nearest neighbor algorithm (ratio 1:1), adjusting for age, sex, arterial hypertension, diabetes, depressed left ventricular ejection fraction, coronary artery disease, history of stroke, AF ablation, CHA2DS2-VASc score, chronic kidney disease and duration of AF episode. The primary endpoint was restoration of sinus rhythm in the emergency department. Results The study population (mean age of 67 (59; 74) years; 53.7% females) was characterized by median AF episode duration of 10.5 (5; 24) hours. Antazoline alone was administered in 23.4% of patients (n=118); amiodarone in 47.5% (n=240); propafenone in 9.9% (n=50); while 19.2% (n=97) received ≥2 antiarrhythmic drugs. Before PSM adjustment, antazoline had comparable rhythm conversion rate to propafenone (85.6% vs. 80.0%; P=0.367) and higher than amiodarone treatment (vs. 66.7%, P=0.0002), and greater than combined amiodarone/propafenone group (68.6%; RR 1.25; 95% CI: 1.12–1.39, P=0.0001). After PSM, the use of antazoline was associated with the efficacy similar to propafenone (82.2% vs. 80.0%, RR 1.03; 95% CI: 0.84–1.25, P=0.788) and superior to amiodarone (85.3% vs. 67.0%, RR 1.27, 95% CI: 1.09–1.48, P=0.0019, number needed to treat 5.5; Figure). No major adverse actions were reported in the antazoline group. Conclusion Antazoline appears to be an efficacious and safe drug for pharmacological cardioversion of AF in real-life setting, which is at least non-inferior to existing antiarrhythmic drugs. Acknowledgement/Funding None

The aim of this study was to develop magnetic molecularly imprinted nano-conjugate sorbent for effective dispersive solid phase extraction of antazoline (ANT) and its metabolite, hydroxyantazoline (ANT-OH) in analytical method employing liquid chromatography coupled with mass spectrometry method. The core–shell material was characterized in terms of adsorption properties, morphology and structure. The heterogeneous population of adsorption sites towards ANT-OH was characterized by two Kd and two Bmax values: Kd (1) = 0.319 µg L−1 and Bmax (1) = 0.240 μg g−1, and Kd (2) = 34.6 µg L−1 and Bmax (2) = 5.82 μg g−1. The elemental composition of magnetic sorbent was as follows: 17.55, 37.33, 9.14, 34.94 wt% for Si, C, Fe and O, respectively. The extraction protocol was optimized, and the obtained results were explained using theoretical analysis. Finally, the analytical method was validated prior to application to pharmacokinetic study in which the ANT was administrated intravenously to three healthy volunteers. The results prove that the novel sorbent could be useful in extraction of ANT and ANT-OH from human plasma and that the analytical strategy could be a versatile tool to explain a potential and pharmacological activity of ANT and ANT-OH.

INTRODUCTION Numerous studies described the effectiveness and safety of antazoline in pharmacological cardioversion of short‑duration atrial fibrillation (AF). However, there are no data on the comparison of antazoline and antiarrhythmic drugs listed in clinical guidelines. OBJECTIVES The aim of the study was to assess the comparative effectiveness and safety of antazoline‑based and propafenone‑based strategies in pharmacological cardioversion of short‑duration AF performed in our emergency department. PATIENTS AND METHODS We conducted a retrospective case‑control study based on the analysis of medical records of patients undergoing pharmacological cardioversion of short‑duration AF with intravenous antazoline or propafenone at our department in the years 2008-2012. The primary endpoint was the successful cardioversion of AF. The primary safety endpoint was hospitalization due to the adverse effects of the treatment. RESULTS We analyzed 432 cases of cardioversion. The mean age of patients was 68.9 ±9.8 years; 65% of the patients were male; 90% of the patients had a history of AF. Antazoline was administered 334 times and propafenone-98 times. The mean dose of antazoline was 172 ±65 mg, while all patients in the propafenone group received the drug at a fixed dose of 70 mg (1 vial). Cardioversion with antazoline was successful in 239 cases (71.6%) and with propafenone-in 54 patients (55.1%) (relative risk [RR], 1.30; 95% confidence interval [CI], 1.07-1.57). The rate of hospitalization due to the adverse effects of the treatment were low and similar between the study groups: 10 (3.0%) for antazoline and 4 (4.1%) for propafenone (RR, 0.73; 95% CI, 0.23-2.27). CONCLUSIONS The antazoline‑based strategy was more effective and safer in comparison with propafenone‑based strategy in the pharmacological cardioversion of short‑duration AF in our emergency department.

Purpose Antazoline is a first-generation antihistaminic agent with additional anticholinergic properties and antiarrhythmic potential. Recent data shows its high effectiveness in sinus rhythm restoration among patients with paroxysmal atrial fibrillation. The effect of antazoline on electrophysiological parameters of the heart in vivo has not yet been examined. The aim of this study was to evaluate changes in electrophysiological parameters of the heart muscle and conduction system as a response to increasing doses of antazoline. Methods After successful ablation of supraventricular arrhythmias, the electrophysiological parameters: sinus rhythm cycle length (SRCL), AH, HV, QRS, QT, QTc intervals, Wenckebach point (WP), sinus node recovery period (SNRT), intra- (hRA-CSos) and interatrial conduction time (hRA-CSd), right and left atrium refractory period (RA-; LA-ERP), and atrioventricular node refractory period (AVN-ERP) were assessed initially and after 100, 200, and 300 mg of antazoline given intravenously. Results Fifteen patients (8 males, 19–72 years old) undergoing EPS and RF ablation were enrolled. After 100 mg bolus, a significant reduction in SRCL was noticed. After antazoline administration, significant prolongation of HV, QRS, QTc, hRA-CSos, hRA-CSd intervals, RA– and LA-ERP and reduction of SRCL were observed. After a total dose of 300 mg, QT interval prolonged significantly. Increasing the dose of antazoline had no impact on AH, Wenckebach point, AVN-ERP, and SNRT. Conclusion Antazoline has an effect on electrophysiological parameters of the atrial muscle and has rapid onset of action. No negative effect on sinus node function and atrioventricular conduction in a unique property among antiarrhythmic drugs.

Degradation of the drug antazoline was studied in aqueous solutions by means of pH-rate profiling (pH 0–7.4). The novel approach of Runge–Kutta numerical integration in combination with multi-parameter optimisation was applied to UV-Vis spectral data to determine a valid kinetic model and kinetic parameters of the degradation process. The overall degradation mechanism was found to be dependent on the environmental pH. In the pH range of 3.0–7.4, the formation of the antazoline hydrolysis product (N-(2-aminoethyl)-2-(N-benzylanilino)acetamide) through three different pathways (acidic, non-catalysed, and semi-alkaline hydrolysis) was observed. In highly acidic media (pH 0–2), the degradation mechanism was found to be more complex. Although the same primary degradation product formed, a colourful (dark blue/violet) intermediate was also observed and further investigated by HPLC/TOF-MS.

Aims Antazoline is a first-generation antihistamine with antiarrhythmic properties. This study examines potential electrophysiological effects of antazoline in short-QT-syndrome (SQTS) and long-QT-syndrome (LQTS). Methods and results Sixty-five rabbit hearts were Langendorff-perfused. Action potential duration at 90% of repolarization (APD90), QT-interval, spatial dispersion (DISP), and effective refractory period (ERP) were measured. The IK, ATP-opener pinacidil (1 µM, n = 14) reduced APD90 (-14 ms, P

Background and aim: To assess safety and efficacy of antazoline for termination of atrial fibrillation (AF) occurring during ablation of accessory pathways (AP). Methods: We analyzed electrophysiological mechanism of antazoline (changes in A-A interval) and the percentage of pre-excited QRS complexes before and after antazoline administration. The total dose administered and the time from the start of injection to sinus rhythm restoration were also measured. Results: Out of consecutive 290 patients with Wolff-Parkinson-White syndrome undergoing radiofrequency (RF) ablation, 12 (4.1%) (4 females, mean age 36 ± 20 years) developed sustained AF which did not stop spontaneously within 10 min, and antazoline in 100 mg repeated boluses was administered. In all 12 patients the drug restored sinus rhythm after a mean of 425 ± 365 s (range 43–1245 s) using a mean cumulative dose of 176 ± 114 mg (range 25–400 mg). The drug slightly prolonged R-R intervals during AF (from 383 ± 106 to 410 ± 70 ms) and reduced the percentage of fully pre-excited QRS complexes (from 35% to 26%). Intracardiac recordings showed gradual increase in A-A intervals, as well as regularization and decreasing fractionation of atrial activity following drug injection (mean A-A interval of 162 ± 30 ms at baseline vs. 226 ± 26 ms shortly before sinus rhythm restoration, p < 0.001). AP was not completely blocked in any patient which enabled continuation of ablation. Conclusions: Antazoline safely and rapidly converts AF into sinus rhythm during ablation of AP. The drug does not block AP completely, enabling continuation of ablation. The drug converting AF into more organized atrial activity (atrial flutter/tachycardia) before sinus rhythm resumption.

Introduction The antihistaminic antazoline (ANT) was reported to be highly effective and safe for rapid conversion of atrial fibrillation (AF). We therefore analyzed underlying mechanisms in an experimental whole-heart model. Methods and Results Isolated and retrogradely perfused rabbit hearts underwent a standardized protocol employing atrial burst pacing induced AF in 5 of 20 hearts under baseline conditions (7 episodes). Thereafter, a combination of acetylcholine and isoproterenol was employed to enhance AF occurrence. Two monophasic action potential recordings on the left- and two on the right atrial epicardium showed a decrease of atrial action potential duration (aAPD, -25ms, p

Different HPLC chromatographic systems were investigated on a C18ACE 5 μm, 150 × 4.6 mm id column for the determination of tymazoline, tramazoline, and antazoline, with either naphazoline or xylometazoline, in commercial preparations. For the development and optimization of the systems, a Response Surface Method (r = 0.925–0.980) was used to illustrate the changes in k as a function of pH values and different salt concentrations. The simultaneous separation of 2-imidazolines was accomplished at 40°C with 0.01 M ammonium acetate–methanol (50 + 50, v/v, pH 6.0) mobile phase at a flow rate of 1.2 mL/min. In order to deal with the usual coexistence of 2-imidazolines with benzethonium and benzalkonium chloride preservatives, it was necessary to use another chromatographic system, 0.01 M ammonium acetate–methanol (50 + 50, v/v) mobile phase on a cyano ACE 5 μm, 150 × 4.6 mm id column. As part of a more thorough theoretical investigation, a partial least-squares (PLS) technique was used for modeling the RP-HPLC retention data. The model was based on molecular structure descriptors of the analytes' X variables and on their retention time (Log K) Y. The goodness of fit was estimated by the PLS correlation coefficient (r2) and root mean square error of estimation values, which were 0.994 and 0.0479, respectively.

Modulation of metabolic activity of phagocytes by antihistaminesThe purpose of the study was to investigate the effects of H1-antihistamines of the 1stgeneration (antazoline, bromadryl, brompheniramine, dithiaden, cyclizine, chlorcyclizine, chlorpheniramine, clemastine) and the 2ndgeneration (acrivastine, ketotifen, and loratadine) on the respiratory burst of phagocytes. Reactive oxygen species generation in neutrophils isolated from rat blood was measured using luminol-enhanced chemiluminescence. Changes in nitrite formation and iNOS protein expression by RAW 264.7 macrophages were analysed using Griess reaction and Western blotting. The antioxidative properties of drugs in cell-free systems were detected spectrophotometrically, luminometrically, fluorimetrically, and amperometrically. The majority of the H1-antihistamines tested (bromadryl, brompheniramine, chlorcyclizine, chlorpheniramine, clemastine, dithiaden, and ketotifen) exhibited a significant inhibitory effect on the chemiluminescence activity of phagocytes. H1-antihistamines did not show significant scavenging properties against superoxide anion and hydroxyl radical, thus this could not contribute to the inhibition of chemiluminescence. H1-antihistamines had a different ability to modulate nitric oxide production by LPS-stimulated macrophages. Bromadryl, clemastine, and dithiaden were the most effective since they inhibited iNOS expression, which was followed by a significant reduction in nitrite levels. H1-antihistamines had no scavenging activity against nitric oxide. It can be concluded that the effects observed in the H1-antihistamines tested are not mediated exclusively via H1-receptor pathway or by direct antioxidative properties. Based on our results, antihistamines not interfering with the microbicidal mechanisms of leukocytes (antazoline, acrivastine and cyclizine) could be used preferentially in infections. Other antihistamines should be used, under pathological conditions accompanied by the overproduction of reactive oxygen species.

Introduction Options for a pharmacological cardioversion (CV) of short-duration atrial fibrillation (AF) in patients with a stable coronary artery disease (CAD) are limited to amiodarone or vernakalant. Antazoline has been reported to achieve high rates of AF conversion to sinus rhythm, but data on its effectiveness and, more importantly, safety in stable CAD patients, have been sparse. Aims To assess the effectiveness and safety of antazoline-based therapy in patients with a stable CAD undergoing pharmacological CV of short-duration AF in the emergency department (ED). Results A retrospective case-control study. We conducted an analysis of medical records of patients with a stable CAD undergoing CV of short duration (≤48 hours) AF in the ED using intravenous antazoline. The main endpoints of the study were successful cardioversion of AF and hospitalization due to the adverse effects (AE) of the treatment. Between 2008 and 2012, out of 548 CVs, antazoline was administered 334 times: 138 in CAD and 196 in the control group. Patients in the CAD group were older and had more comorbidities than controls; 65 patients had had a history of myocardial infarction (MI). In CAD group, the effectiveness was higher (82.6% vs 63.8%, RB: 1.30 [95% CI: 1.14-1.48], P = 0.0002) and the hospitalization rate due to AE was similar (1.4% vs 4.1%, RR: 0.36 [95% CI: 0.08-1.65], P = 0.2054) to the control group. Among patients with CAD, a history of MI did not influence the effectiveness or safety of the CV (P = 0.2252 and P = 1.0000, respectively). Conclusions In selected patients with a stable CAD, even with a history of MI, antazoline-based CV of short-duration AF may be an effective and safe therapeutic option.

Ratio derivative spectrophotometrie method has been developed for the simultaneous determination of naphazoline (NAP) and antazoline (ANT) at micromolar levels in Britton Robinson buffer (pH 9) medium. In this method the overlapping spectra of naphazoline and antazoline were well resolved by making use of the first-derivative of the ratios of their direct absorption spectra. The derivative ratio absorbances of naphazoline and antazoline were measured at 227.2 and 235 nm, respectively for their quantification. The method is simple, fast and does not require separation of naphazoline and antazoline. Another salient feature of the method is that simultaneous standard additions of both analytes permitted to resolve matrix effect and quantification at a unique standard addition plot. Naphazoline and antazoline were determined in the concentration range of 10-150 μmol L-1(NAP/ANT ratio varying from about 10 to 150) in the same aliquot with a precision and accuracy of about 1.7% and 1.8%, respectively. The recommended procedure was successfully applied for analysis of naphazoline and antazoline in eye drops.

A zero-crossing first-derivative spectrophotometric method is applied for the simultaneous determination of naphazoline hydrochloride and antazoline phosphate in eye drops. The measurements were carried out at wavelengths of 225 and 252 nm for naphazoline hydrochloride and antazoline phosphate, respectively. The method was found to be linear (r2>0.999) in the range of 0.2-1 microg/ml for naphazoline hydrochloride in the presence of 5 microg/ml antazoline phosphate at 225 nm. The same linear correlation (r2>0.999) was obtained in the range of 1-10 microg/ml of antazoline phosphate in the presence of 0.5 microg/ml of naphazoline hydrochloride at 252 nm. The limit of determination was 0.2 microg/ml and 1 microg/ml for naphazoline hydrochloride and antazoline phosphate, respectively. The method was successfully used for simultaneous analysis of naphazoline hydrochloride and antazoline phosphate in eye drops without any interference from excipients and prior separation before analysis.

Background Antazoline is an old antihistaminic and new antiarrhythmic agent with unknown mechanisms of action which recently has been shown to effectively terminate atrial fibrillation. The aim of study was to examine the effects of antazoline on hemodynamic and ECG parameters. Methods Antazoline was given intravenously in three 100 mg boluses to 10 healthy volunteers (four males, mean age 40 + 11 years). Hemodynamic and ECG parameters were measured using impedance cardiography [systolic (sBP), diastolic (dBP), mean (mBP) blood pressure, stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and heart rate (HR), P wave, PR interval, QRS complex, QT and corrected QT (QTcF) interval]. Plasma concentration of antazoline was also measured. Results Antazoline caused significant prolongation of P wave, QRS as well as QT and QTcF (101 ± 10 vs 110 ± 16 ms, p

A novel net analyte signal standard addition method (NASSAM) was used for simultaneous determination of the drugs anthazoline and naphazoline. The NASSAM can be applied for determination of analytes in the presence of known interferents. The proposed method is used to eliminate the calibration and prediction steps of multivariate calibration methods; the determination is carried out in a single step for each analyte. The accuracy of the predictions against the H-point standard addition method is independent of the shape of the analyte and interferent spectra. The net analyte signal concept was also used to calculate multivariate analytical figures of merit, such as LOD, selectivity, and sensitivity. The method was successfully applied to the simultaneous determination of anthazoline and naphazoline in a commercial eye drop sample.

1. In rat whole portal veins, guanabenz (100 nM to 10 microM) and antazoline (100 nM to 100 microM) each increased the amplitude, frequency and duration of spontaneous contractions. In addition, guanabenz (30 microM) and antazoline (30 microM) each antagonized the ability of levcromakalim (3 nM to 10 microM) to inhibit the spontaneous contractions of this tissue. 2. Whole-cell voltage-clamp recordings were made from freshly-isolated rat portal vein cells dispersed by a collagenase/pronase enzyme treatment. The ability of several agents (antazoline, cirazoline, clonidine, guanabenz and phentolamine, each containing an imidazoline or guanidine moiety), to modulate potassium (K) currents and to inhibit the actions of levcromakalim was investigated. 3. Antazoline, cirazoline, clonidine, guanabenz and phentolamine (each at a concentration of 30 microM) had little effect on control non-inactivating currents but inhibited the delayed-rectifier current, IK(V). 4. Levcromakalim (1 microM) induced a non-inactivating current, IK(ATP), and also inhibited the delayed rectifier current, IK(V). 5. Glibenclamide (1 microM) had no effect on control delayed rectifier or non-inactivating currents, but it inhibited the simultaneous induction of IK(ATP) and reduction of IK(V) produced by levcromakalim (1 microM). 6. Antazoline, cirazoline, clonidine and guanabenz (each at a concentration of 30 microM) prevented the induction of IK(ATP) by levcromakalim (1 microM). Phentolamine (30 microM) and clonidine (30 microM) each inhibited the IK(ATP) generated by levcromakalim (1 microM). 7. It is concluded that a variety of agents which possess either an imidazoline (antazoline, cirazoline, clonidine and phentolamine) or a guanidine (guanabenz) moiety within their structure inhibit the delayed rectifier current, IK(V). This action may thus be mediated via a so-called non-adrenoceptor imidazoline binding site. Furthermore, the ability of these ligands to inhibit IK(V) and to antagonize both the induction of IK(ATP) and the vasorelaxation produced by levcromakalim is consistent with the view that the channel (KATP) which underlies IK(ATP) is a voltage-insensitive state of the delayed rectifier K-channel (Kv).