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Little is known about the effectiveness of pharmacological cardioversion (PCV) with antazoline in comparison to flecainide. The aim of this study was to compare the effectiveness of antazoline in restoring sinus rhythm (SR) versus amiodarone, flecainide and propafenone in a group of emergency department (ED) patients. This was a single-centre retrospective analysis of patient records from an ED in a large hospital in Poland. We analysed a total of 1878 patient records, divided based on the anti-arrhythmic drug (AAD) administered during PCV: antazoline (n ​= ​1080), antazoline ​+ ​β-blocker (n ​= ​479), amiodarone (n ​= ​129), flecainide (n ​= ​102), propafenone (n ​= ​88). Of the patients, 63.5 ​% were female (median 65 years, [19–100]). The percentage of successful PCV was significantly higher in the antazoline group (84.3 ​%) than in the antazoline ​+ ​β-blocker (75.8 ​%, p ​= ​0.0001), propafenone (75.6 ​%, p ​= ​0.0364) and amiodarone (68.8 ​%, p ​< ​0.0001) groups. Post-hoc analysis revealed that patients who received PCV with antazoline, antazoline ​+ ​β-blocker, flecainide and propafenone had significantly shorter time to SR than those who received amiodarone (p ​< ​0.0001). Univariate regression analysis revealed that patients who underwent PCV with antazoline were almost twice as likely to return to SR compared to the other groups (p ​< ​0.0001, OR 1.81, 95 ​% CI 1.44–2.27). This is the first study comparing the effectiveness of antazoline in PCV versus flecainide in addition to the previously studied amiodarone and propafenone. Our results indicate that antazoline is more effective in restoring SR than amiodarone, flecainide and propafenone. In addition, antazoline restored SR significantly faster than amiodarone or propafenone. [ABSTRACT FROM AUTHOR]

A novel spectrofluorimetric method has been developed for determination of antazoline (ANT) and tetryzoline (TET) in their pharmaceutical formulation. A combined application of synchronous spectrofluorimetry and second derivative mathematical treatment was developed. The proposed method depends on reacting the cited drugs with dansyl chloride (DNS‐Cl) being a suitable derivatizing agent generating highly fluorescent derivatives measured at emission wavelengths of 703.0 and 642.0 nm after excitation wavelengths of 350.0 and 320.0 nm for ANT and TET, respectively. The joint use of synchronous spectrofluorimetry with second derivative mathematical treatment is for the first time to be developed and optimized in aid of using fluorescence data manager software generating second derivative peak amplitudes at 556.5 nm for ANT and 516.7 nm for TET. Linear responses have been represented over a wide range of concentration (0.5–12.0 μg/mL for ANT and 0.5–10.0 μg/mL for TET). Additionally, statistical comparison of the developed method with the official ones has been carried out where no significant difference was found. Additionally, greenness profile assessment was accomplished by means of four metric tools. Indeed, the method developed is found to be precise, sensitive, and discriminating to assess the cited drugs for regular analysis. [ABSTRACT FROM AUTHOR]

Introduction: Antazoline with propafenone may be an alternative to electrical cardioversion (ECV) in restoring sinus rhythm in patients with atrial fibrillation (AF), including during balloon cryoablation. Aim: To compare the efficacy of antazoline with propafenone and ECV in restoring and maintaining sinus rhythm at discharge in patients with AF during cryoablation with special regard to type of AF. Material and methods: The study retrospectively analyzed 196 patients who underwent elective cryoablation. Eighty-nine patients who developed AF in the perioperative period were selected as the study group (32 women and 57 men). The study group was divided into two groups – 46 (51.7%) patients were given pharmacological cardioversion with 70 mg of propafenone and 100 or 200 mg of antazoline, whereas the other 43 (48.3%) patients underwent ECV. Results: There were no statistically significant differences between the groups regarding: left atrial area, left atrium diameter, right atrial area and right atrium diameter. In the overall population, ECV was more effective than antazoline with propafenone therapy (31 [72.1%] vs. 20 [43.5%]; p = 0.01). A similar relationship was demonstrated in patients with persistent AF (13 [59.1%] vs. 3 [12.5%]; p = 0.002). There was no significant difference in the group of patients with paroxysmal AF (18 (85.6%) vs. 17 (77.3%); p = 0.7). Conclusions: In AF during the cryoablation procedure ECV appears to be more effective in restoring and maintaining sinus rhythm at discharge than antazoline with propafenone in the general AF patient population, especially in patients with persistent AF. [ABSTRACT FROM AUTHOR]

Context: In the emergency department, patients with recent-onset atrial fibrillation are typically managed with intravenous antiarrhythmic agents. However, the currently used agents have a low efficacy and safety profile. Antazoline is an antihistaminic agent that has been shown to have a strong antiarrhythmic effect when administered intravenously, facilitating rapid conversion to normal sinus rhythm. Aims: To systematically review the literature on the safety and efficacy of antazoline in the treatment of recent-onset short-duration atrial fibrillation and to compare the clinical efficacy of antazoline to that of other antiarrhythmic agents listed in clinical guidelines. Methods: The study was written in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. A comprehensive search of databases (PubMed, Scopus, ScienceDirect, Web of Sciences, Google Scholar, Clinical trial.gov) for relevant studies in English from inception to 2021 using keywords involving “antazoline” AND other terms such as “antiarrhythmic”, “atrial fibrillation”, and “arrhythmia”. Results: Of the 478 studies identified, 446 were screened, and 7 were included, one of which was a randomized control trial, and the others were observational studies. The majority of studies indicated that antazoline resulted in rapid cardioversion to sinus rhythm. When compared to other pharmacological cardioversion options, antazoline achieved higher cardioversion rates than amiodarone or propafenone and was generally a safer option. Conclusions: Antazoline appears to be an effective pharmacological agent for the rapid cardioversion of short-term atrial fibrillation. More randomized clinical trials, however, should be conducted to strengthen the evidence.

Ophthalmic pharmaceutical preparation containing antazoline hydrochloride (ANT) and tetryzoline hydrochloride (TET) is prescribed widely as an over the counter (OTC) medication to treatment allergic conjunctivitis and their determination in presence of their degradation products is a major challenge. A novel sensitive, selective, and precise thin-layer chromatographic method established to determination both ANT and TET in both bulk drugs, formulation, and in presence of their degradation products with the elucidation of degradate's structures. Upon using silica gel plates and means of a developing system using ethyl acetate: ethanol: ammonia (8: 2: 0.1, by volume) the studied drugs separation was achieved, and scanning was carried out at 220.0 nm for the separated bands with a 0.2–18.0 µg/band concentration range for each of ANT and TET. Optimum separation was achieved with values Rf of 0.42 and 0.69, for TET and ANT, respectively. Additionally, the studied drugs' stock solutions were imperiled to different stress conditions. Both drugs were found to be vulnerable to alkaline hydrolysis as well as oxidative degradation showing well resolved degradation products' peaks. While they held out against acidic, thermal and photo degradation. Mass spectrometry was employed to elucidate the degradates' structures. Validity was applied for the proposed method with respect to all validation parameters. Effectively the method was applied to estimate the cited drugs' in marketed ophthalmic formulation.

Antazoline is an antihistaminic drug that is effective in the termination of paroxysmal atrial fibrillation. Despite its long presence in the market, antazoline's ADME parameters and pharmacokinetic effects in humans are poorly characterized. The objective of this study was to fill this gap by generation of in vitro and in vivo data and the development of a physiologically based pharmacokinetic model describing antazoline and its main metabolite disposition. A set of ADME parameters for the antazoline and its hydroxy metabolite is provided based on literature data, QSAR predictions, in vitro binding and metabolic stability assays. These can be used to feed PBPK models. In our current work, the developed PBPK model simulating simultaneously the pharmacokinetic profile of antazoline and its metabolite was successfully verified against the available clinical data and the presented capability to account for the clinically observed variability. When used to feed the PD model (e.g., simulating ECG), concentration-time profiles predicted by the model enable the assessment of antazoline's effect in various clinical scenarios with the possibility to account for population differences or CP mediated drug-drug interactions. [ABSTRACT FROM AUTHOR]

Antazoline is an antihistaminic drug that is effective in the termination of paroxysmal atrial fibrillation. Despite its long presence in the market, antazoline’s ADME parameters and pharmacokinetic effects in humans are poorly characterized. The objective of this study was to fill this gap by generation of in vitro and in vivo data and the development of a physiologically based pharmacokinetic model describing antazoline and its main metabolite disposition. A set of ADME parameters for the antazoline and its hydroxy metabolite is provided based on literature data, QSAR predictions, in vitro binding and metabolic stability assays. These can be used to feed PBPK models. In our current work, the developed PBPK model simulating simultaneously the pharmacokinetic profile of antazoline and its metabolite was successfully verified against the available clinical data and the presented capability to account for the clinically observed variability. When used to feed the PD model (e.g., simulating ECG), concentration-time profiles predicted by the model enable the assessment of antazoline’s effect in various clinical scenarios with the possibility to account for population differences or CP mediated drug-drug interactions.

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. [ABSTRACT FROM AUTHOR]

A novel spectrofluorimetric method has been developed for determination of antazoline (ANT) and tetryzoline (TET) in their pharmaceutical formulation. A combined application of synchronous spectrofluorimetry and second derivative mathematical treatment was developed. The proposed method depends on reacting the cited drugs with dansyl chloride (DNS-Cl) being a suitable derivatizing agent generating highly fluorescent derivatives measured at emission wavelengths of 703.0 and 642.0 nm after excitation wavelengths of 350.0 and 320.0 nm for ANT and TET, respectively. The joint use of synchronous spectrofluorimetry with second derivative mathematical treatment is for the first time to be developed and optimized in aid of using fluorescence data manager software generating second derivative peak amplitudes at 556.5 nm for ANT and 516.7 nm for TET. Linear responses have been represented over a wide range of concentration (0.5-12.0 μg/mL for ANT and 0.5-10.0 μg/mL for TET). Additionally, statistical comparison of the developed method with the official ones has been carried out where no significant difference was found. Additionally, greenness profile assessment was accomplished by means of four metric tools. Indeed, the method developed is found to be precise, sensitive, and discriminating to assess the cited drugs for regular analysis., (© 2024 John Wiley & Sons Ltd.)

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 CHA2DS2‐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. [ABSTRACT FROM AUTHOR]

Background Antazoline mesylate represents an antihistamine capable of rapid and safe cardioversion of atrial fibrillation, yet evidence concerning its efficacy in comparison to other medications is insufficient. The study aimed to evaluate the success rate and safety of pharmacological cardioversion of atrial fibrillation with intravenous antazoline (CANT [Cardioversion With Antazoline Mesylate] study) in the setting of the emergency department. Methods and Results After reviewing 1984 medical records, 450 eligible patients (22.7%) with short‐duration atrial fibrillation subject to pharmacological cardioversion were enrolled in a retrospective observational analysis. The choice of antiarrhythmic drug was left to the discretion of the attending physician. The primary end point was successful cardioversion in the emergency department. The safety end point comprised bradycardia

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 < 0.01), QT-interval (-14 ms, P < 0.01), and ERP (-11 ms, P < 0.01), thus simulating acquired SQTS. Additional infusion of 20 µM antazoline prolonged repolarization. Under baseline conditions, ventricular fibrillation (VF) was inducible in 5 of 14 hearts (10 episodes) and in 5 of 14 pinacidil-treated hearts (21 episodes, P = ns). Antazoline significantly reduced induction of VF (0 episodes, P < 0.05 each). Further 17 hearts were perfused with 100 µM sotalol and 17 hearts with 300 µM erythromycin to induce acquired LQTS2. In both groups, prolongation of APD90, QT-interval, and ERP was observed. Spatial dispersion was increased (sotalol: +26 ms, P < 0.01; erythromycin: +31 ms, P < 0.01). Additional infusion of antazoline reduced DISP (sotalol: -22 ms, P < 0.01; erythromycin: -26 ms, P < 0.01). Torsade de pointes (TdP) occurred in 6 of 17 sotalol-treated (22 episodes, P < 0.05 each) and in 8 of 17 erythromycin-treated hearts (96 episodes P < 0.05 each). Additional infusion of antazoline completely suppressed TdP in both groups (P < 0.05 each). Acquired LQTS3 was induced by veratridine (0.5 µM, n = 17) and similar results were obtained (APD90: +24 ms, P < 0.01, QT-interval: +58 ms, P < 0.01, DISP: +38 ms, P < 0.01). Torsade de pointes occurred in 10 of 17 hearts (41 episodes, P < 0.05 each). Antazoline significantly reduced TdP (2 of 17 hearts, 4 episodes, P < 0.05 each).Conclusion: Antazoline significantly reduced induction of VF in an experimental model of acquired SQTS. In three experimental models of acquired LQTS, antazoline effectively suppressed TdP. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This work implements a stability indicating HPLC method developed to simultaneously determine xylometazoline (XYLO) and antazoline (ANT) in their binary mixture, rabbit aqueous humor and cited drug's degradates by applying analytical quality-by-design (AQbD) combined with green analytical chemistry (GAC) experiment for the first time. This integration was designed to maximize efficiency and minimize environmental impacts, as well as energy and solvent consumption. Analytical quality-by-design was applied to achieve our aim starting with evaluation of quality risk and scouting analysis, tracked via five parameters chromatographic screening using Placket-Burman design namely: pH, temperature, organic solvent percentage, flow rate, and wavelength detection. Recognizing the critical method parameters was done followed by optimization employing central composite design and Derringer's desirability toward assess optimum conditions that attained best resolution with satisfactory peak symmetry with short run time. Optimal chromatographic separation was attained by means of an XBridge® C18 (4.6 × 250 mm, 5 µm) column through isocratic elution using a mobile phase consists of phosphate buffer (pH 3.0): ethanol (60:40, by volume) at a 1.6 mL/min flow rate and 230.0 nm UV detection. Linearity acquired over a concentration range of 1.0–100.0 µg/mL and 0.5–100.0 µg/mL for XYLO and ANT, respectively. Furthermore, imperiling cited drugs' stock solutions to stress various conditions and satisfactory peaks of degradation products were obtained indicating that cited drugs are vulnerable to oxidative degradation and basic hydrolysis. Degradates' structures were elucidated using mass spectrometry. Applying various assessment tools; namely: analytical greenness (AGREE), green analytical procedure index (GAPI), analytical eco-scale, and national environmental method index (NEMI), Greenness method's evaluation was applied and proved to be green. In fact, the developed method is established to be perceptive, accurate, and selective to assess cited drugs for routine analysis. [Display omitted] • Stability indicating HPLC method to determine xylometazoline and antazoline. • Analysis of the studied drugs in rabbit aqueous humor samples was done. • An integration between AQbD approach and GAC principles was achieved. • Structure elucidation for the degradants was done using mass spectrometry. • Greenness profile assessment was accomplished via four smart metric tools. [ABSTRACT FROM AUTHOR]

Aims: The aim of the study was to assess the clinical efficacy of antazoline, a first-generation anti-histaminic agent, in the rapid conversion of paroxysmal non-valvular atrial fibrillation (AF) to sinus rhythm in patients without heart failure.Methods and Results: This study was a single center, randomized, double blind, placebo-controlled, superiority clinical trial. We enrolled patients with an AF episode lasting less than 43 h, in stable cardiopulmonary condition. Subjects who fulfilled the selection criteria were randomly assigned to receive intravenously either a placebo or up to 250 mg of antazoline. The primary end point was the conversion of AF to sinus rhythm confirmed in electrocardiogram (ECG). We enrolled 74 patients: 36 (48.6%) in the antazoline group and 38 (51.4%) in the control group. The mean age was 68 ± 12 years (range 31-90 years), 39 (53.3%) patients were male. The successful conversion of AF to sinus rhythm during the observation period was achieved in 26 (72.2%) patients treated with antazoline and 4 (10.5%) in the control group: RR 6.86 (95% CI: 2.66-17.72, P < 0.0001). Median time to conversion was 16.0 min in antazoline and 72.5 min in the control group (P = 0.0246). There were no cases of atrial tachycardia/flutter in the antazoline group.Conclusion: Intravenous antazoline was effective and safe in the rapid conversion of non-valvular paroxysmal atrial fibrillation to sinus rhythm in patients without heart failure. Clinical Trial Registration number: NCT01527279. [ABSTRACT FROM AUTHOR]

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 < .05, and 101 ± 12 vs 107 ± 12 ms, p < .05, 399 ± 27 vs 444 ± 23 ms, p < .05, and 403 ± 21 vs 448 ± 27 ms, p < .05, respectively). Also, a significant decrease in SV was noted (94.9 ± 21.8 vs 82.4 ± 19.6 ml, p < .05). A significant correlation between changes in plasma drug concentration and changes in CO, HR, and dBP was found.Conclusions: Antazoline impairs slightly hemodynamics, significantly reducing SV. Significant prolongation of P wave and QRS duration corresponds to drug-induced prolongation of conduction, whereas QT prolongation represents drug-induced prolongation of repolarization. [ABSTRACT FROM AUTHOR]

In the μresent study, a newly develoμed method based on ultrahigh μerformance liquid chromatograμhy (UHPLC) was oμtimized for the simultaneous determination of antazoline hydrochloride (ANZ) and naμhazoline hydrochloride (NFZ) in oμhthalmic formulations. Isocratic seμaration of ANZ and NFZ was μerformed at 40 °C with an ACE Excel 2 Cl8-PFP column (2 μm, 2.1 x 100 mm) at a flow rate of 0.6 mL min-1 whereas the mobile μhase consisted of acetonitri-le/μhosμhate buffer (60:40, v/v, μH 3.0) containing 0.5% triethylamine. Both analytes were detected at a wavelength of 285 nm and the injection volume was 1.0 μL. The overall run time μer samμle was 4.5 min with retention time of 0.92 and 1.86 min for NFZ and ANZ, resμectively. The calibration curve was linear from 0.500-100 μg mL-1 for ANZ and NFZ with a correlation coefficient ≥ 0.9981 while reμeatability and reμroducibility (exμressed as relative standard deviation) were lower than 1.28 and 2.14%, resμectively. In comμarison with high-μerformance liquid chromatograμhy (HPLC), the develoμed UHPLC method had remarkable advantages over HPLC as the run time was significantly reduced by 3.4-fold with a 5-fold decreased solvent consumμtion. Forced degradation studies indicated a comμlete seμaration of the analytes in the μresence of their degradation μroducts μroviding high degree of method sμecificity. The μroμosed UHPLC method was demonstrated to be simμle and raμid for the determination of ANZ and NFZ in commer-cially available oμhthalmic formulations μroviding recoveries between 99.6 and 100.4%. [ABSTRACT FROM AUTHOR]

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 five of 20 hearts under baseline conditions (seven 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 in atrial action potential duration ( aAPD, −25 msec, P<.05) and atrial effective refractory period ( aERP; −52 msec, P<.01) after infusion of acetylcholine (1 μmol/L) and isoproterenol (1 μmol/L). This led to induction of AF in 14 of 20 hearts (145 episodes). Simultaneous infusion of ANT (20 μmol/L) led to a complete suppression of AF in all inducible hearts. Treatment with ANT also led to a significant increase in aAPD (+41 msec, P<.01) and aERP (+74 msec, P<.05), leading to a marked increase in atrial postrepolarization refractoriness ( aPRR, +33 msec, P<.01). Results were compared to 13 rabbits treated with flecainide. Flecainide induced a significant increase in aPRR and resulted in induction of AF in seven of 13 hearts (51 episodes) while 11 of 13 hearts were inducible with acetylcholine and isoproterenol (93 episodes). Conclusion Administration of ANT was highly effective in suppressing AF. The antiarrhythmic effect could be explained by a significant increase in postrepolarization refractoriness as a result of a more marked increase in aERP as compared with aAPD. [ABSTRACT FROM AUTHOR]

Capillary electrophoretic (CE) and high performance liquid chromatographic (HPLC) methods were developed and optimized for the determination of antazoline (ANT) and tetrahydrozoline (TET) in ophthalmic formulations. Optimum electrophoretic conditions were achieved using a background electrolyte of 20 mM phosphate buffer at pH 7.0, a capillary temperature of 25 °C, a separation voltage of 22 kV and a pressure injection of the sample at 50 mbar for 17 s. HPLC analysis was performed with Kinetex (150 × 4.6 mm ID × 5 μm) (Phenomenex, USA) analytical column with 1 mL min −1 flow rate of mobile phase which consisted of 0.05% TFA in bidistilled water (pH adjusted to 3.0 with 5 M NaOH) and acetonitrile/buffer in the ratio of 63:37 (v/v) at room temperature. Injection volume of the samples was 10 μL and the wavelength of the detector was set at 215 nm for monitoring both analytes. Calibration graphs showed a good linearity with a coefficient of determination (R 2 ) of at least 0.998 for both methods. Intraday and interday precision (expressed as RSD%) were lower than 2.8% for CE and 0.92% for HPLC. The developed methods were demonstrated to be simple and rapid for the determination of ANT and TET in ophthalmic solutions providing recoveries in the range between 97.9 and 102.70% for CE and HPLC. [ABSTRACT FROM AUTHOR]

A comparative study was developed between two classical spectrophotometric methods (dual wavelength method and Vierordt's method) and two recent methods manipulating ratio spectra (ratio difference method and first derivative of ratio spectra method) for simultaneous determination of Antazoline hydrochloride (AN) and Tetryzoline hydrochloride (TZ) in their combined pharmaceutical formulation and in the presence of benzalkonium chloride as a preservative without preliminary separation. The dual wavelength method depends on choosing two wavelengths for each drug in a way so that the difference in absorbance at those two wavelengths is zero for the other drug. While Vierordt's method, is based upon measuring the absorbance and the absorptivity values of the two drugs at their λ max (248.0 and 219.0 nm for AN and TZ, respectively), followed by substitution in the corresponding Vierordt's equation. Recent methods manipulating ratio spectra depend on either measuring the difference in amplitudes of ratio spectra between 255.5 and 269.5 nm for AN and 220.0 and 273.0 nm for TZ in case of ratio difference method or computing first derivative of the ratio spectra for each drug then measuring the peak amplitude at 250.0 nm for AN and at 224.0 nm for TZ in case of first derivative of ratio spectrophotometry. The specificity of the developed methods was investigated by analyzing different laboratory prepared mixtures of the two drugs. All methods were applied successfully for the determination of the selected drugs in their combined dosage form proving that the classical spectrophotometric methods can still be used successfully in analysis of binary mixture using minimal data manipulation rather than recent methods which require relatively more steps. Furthermore, validation of the proposed methods was performed according to ICH guidelines; accuracy, precision and repeatability are found to be within the acceptable limits. Statistical studies showed that the methods can be competitively applied in quality control laboratories. [ABSTRACT FROM AUTHOR]

Background: Data on sex differences in terms of action of antiarrhythmic agents (AADs) are limited. This study aimed to evaluate the clinical profile of patients with atrial fibrillation (AF), and efficacy and safety of AADs used for pharmacological cardioversion (PCV) of AF., Methods: This research was a sub-analysis of the retrospective multicenter Cardioversion with ANTazoline II (CANT) registry, which comprised 1365 patients with short-duration AF referred for urgent PCV with the use of AAD. Patients were categorized according to and compared in terms of clinical parameters and PCV outcomes. The primary endpoint was return of sinus rhythm within 12 hours after drug infusion, and the composite safety endpoint involved bradycardia <45 bpm, hypotension, syncope, or death., Results: The sex distribution of patients qualified for PCV was even (men, n = 725; 53.1%). Females were older and more symptomatic and had higher CHA2DS2-VASc scores, higher prevalence of tachyarrhythmia, and higher use of chronic anticoagulation. The overall efficacy (71.4% vs. 70.1%; P = 0.59) and safety (5.2% vs. 4.6%; P = 0.60) of PCV was comparable in men and women. Amiodarone (68.3% vs. 65.9%; P = 0.66) and antazoline (77.1% vs. 80.0%; P = 0.19) had similar efficacy in men and women, but propafenone had a lower rate of rhythm conversion in men (64.7% vs. 79.3%; P = 0.046). None of the assessed AADs differed in terms of safety profile in both sexes., Conclusion: Female patients with AF have different clinical profiles but similar efficacy and safety of AADs as compared to male participants. Propafenone has significantly lower efficacy in men, which requires further investigation.

Background: Rapid conversion of atrial fibrillation (AF) to sinus rhythm may be achieved by the administration of class IA, IC and III antiarrhythmic drugs or vernakalant hydrochloride. However, that treatment may be related to potential pro-arrhythmia, lack of efficacy or the exceptionally high cost of a compound used. Antazoline is a first generation antihistaminic agent with chinidin-like properties. When administered intravenously, antazoline exerts a strong antiarrhythmic effect on supraventricular arrhythmia, especially on AF, facilitating rapid conversion to sinus rhythm. Despite a relative lack of published data antazoline has been marketed in Poland and widely used in cardiology wards and emergency rooms for many years due to its efficacy, safety and rapid onset of action within minutes of administration. Methods/design: A randomized, double blind, placebo-controlled, superiority clinical trial was designed to assess clinical efficacy of antazoline in rapid conversion of AF to sinus rhythm. Eligible patients will present AF lasting less than 43 hours, will be in stable cardio-pulmonary condition and will have no prior history of advanced heart failure or significant valvular disease. Long-term antiarrhythmic therapy is not considered an exclusion criterion. Subjects who fulfill selection criteria will be randomly assigned to receive intravenously either antazoline or placebo in divided doses and observed for 1.5 hours after conversion to sinus rhythm or after the last i.v. bolus. Primary end point will be the conversion of AF to sinus rhythm confirmed in an electrocardiogram (ECG) during the observation period. Secondary end points will be comprised of time to conversion and return of AF during the observation period. Special consideration will be given to the observation of any adverse events. A sample size of 80 patients was calculated based on the following assumptions: two-tailed test, a type I error of 0.01, a power of 90%, efficacy of placebo 5%, efficacy of antazoline 50% and 20% drop-out rate to fulfill the criteria of intention-to-treat analysis. Due to the presumed lack of statistical power, the secondary end points and safety endpoints will be considered exploratory. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Four imidazoline derivatives: antazoline (AN), naphazoline (NN), tymazoline (TM), xylometazoline (XM), in the form of hydrochlorides in solid phase have been subjected to high energy e-beam irradiation from an accelerator (~10 MeV) at a dose varied from 25 to 200 kGy. The effects of the irradiation have been assessed by DSC, X-ray diffraction, FTIR, EPR and TLC. The standard sterilisation dose of 25 kGy has been found to produce changes in the properties of one derivative (XM), two other ones (AN and TM) have been found sensitive to doses >100 kGy, whereas NN has been resistant to irradiation in the whole range studied (25–200 kGy). EPR results indicated that the changes taking place in the therapeutic substances studied are related to radical formation. The irradiation induced changes in colour, a decrease or increase in the melting point, changes in the XRD pattern, small changes in the shape of FTIR peaks and the presence of radiolysis products. The XM compounds cannot be sterilised by irradiation because of the radiation induced changes in its physico-chemical properties. [ABSTRACT FROM AUTHOR]

Abstract: Net analyte signal (NAS)-based multivariate calibration methods were employed for simultaneous determination of anthazoline and naphazoline. The NAS vectors calculated from the absorbance data of the drugs mixture were used as input for classical least squares (CLS), principal component and partial least squares regression PCR and PLS methods. A wavelength selection strategy was used to find the best wavelength region for each drug separately. As a new procedure, we proposed an experimental design-neural network strategy for wavelength region optimization. By use of a full factorial design method, some different wavelength regions were selected by taking into account different spectral parameters including the starting wavelength, the ending wavelength and the wavelength interval. The performance of all the multivariate calibration methods, in all selected wavelength regions for both drugs, was evaluated by calculating a fitness function based on the root mean square error of calibration and validation. A three-layered feed-forward artificial neural network (ANN) model with back-propagation learning algorithm was employed to model the nonlinear relationship between the spectral parameters and fitness of each regression method. From the resulted ANN models, the spectral regions in which lowest fitness could be obtained were chosen. Comparison of the results revealed that the net NAS-PLS resulted in lower prediction error than the other models. The proposed NAS-based calibration method was successfully applied to the simultaneous analyses of anthazoline and naphazoline in a commercial eye drop sample. [Copyright &y& Elsevier]

Experimental studies have indicated that the central histaminergic system plays an important role in the inhibition of seizures through the stimulation of histamine H1 receptors. H1 receptor antagonists, including classical antiallergic drugs, occasionally may induce convulsions in healthy children and patients with epilepsy. The purpose of this study was to investigate the effects of antazoline and ketotifen (two H1 receptor antagonists) on the anticonvulsant activity of antiepileptic drugs against maximal electroshock (MES)-induced convulsions in mice. The following antiepileptic drugs were used: valproate, carbamazepine, diphenylhydantoin and phenobarbital. In addition, the effects of antiepileptic drugs alone or in combination with antazoline or ketotifen were studied on long-term memory (tested in the passive avoidance task) and motor performance (evaluated in the chimney test), acutely and after 7-day treatment with these H1 receptor antagonists. The influence of antazoline and ketotifen on the free plasma and brain levels of the antiepileptics was also evaluated.Antazoline (at 0.5 mg/kg), given acutely and after 7-day treatment, significantly diminished the electroconvulsive threshold. Similarly, ketotifen, after acute and chronic doses of 8 mg/kg markedly reduced the threshold for electroconvulsions. In both cases, antazoline and ketotifen were without effect upon this parameter at lower doses. Antazoline (0.25 mg/kg) significantly raised the ED50 value of carbamazepine against MES (both, acutely and after 7-day treatment). Furthermore antazoline (0.25 mg/kg) also reduced the anticonvulsant activity of diphenylhydantoin, but only after repeated administration, without modifying the brain and free plasma level of this drug. Moreover, valproate and phenobarbital did not change their protective activity when combined with antazoline. Ketotifen (4 mg/kg) possessed a biphasic action, acutely it enhanced the anticonvulsant action of carbamazepine and phenobarbital while, following 7-day treatment, reduced the antiseizure activity of carbamazepine. Ketotifen did not affect the free plasma or brain levels of antiepileptics tested. Only acute antazoline (0.25 mg/kg) applied with valproate impaired the performance of mice evaluated in the chimney test. Ketotifen (4 mg/kg) co-administered with conventional antiepileptic drugs impaired motor coordination in mice treated with valproate, phenobarbital or diphenylhydantoin. Acute and chronic antazoline (0.25 mg/kg) alone or in combination with antiepileptic drugs did not disturb long-term memory, tested in the passive avoidance task. Similarly, ketotifen (4 mg/kg) did not impair long-term memory, acutely and after 7-day treatment. However, valproate alone or in combination with chronic ketotifen (4 mg/kg) worsened long-term memory. The results of this study indicate that H1 receptor antagonists, crossing the blood brain barrier, should be used with caution in epileptic patients. This is because antazoline reduced the protective potential of diphenylhydantoin and carbamazepine. Also, ketotifen reduced the protection offered by carbamazepine and elevated the adverse activity of diphenylhydantoin, phenobarbital and valproate. [Copyright &y& Elsevier]

The mixed dissociation constants of five drug acids—ambroxol, antazoline, naphazoline, oxymetazoline and ranitidine—at various ionic strengths I of range 0.01 and 1.0 and at temperatures of 25 and 37 °C were determined using SQUAD(84) regression analysis of the pH-spectrophotometric titration data. A proposed strategy of efficient experimentation in a protonation constants determination, followed by a computational strategy for the chemical model with a protonation constants determination, is presented on the protonation equilibria of ambroxol. The thermodynamic dissociation constant pKaT was estimated by non-linear regression of {pKa, I} data at 25 and 37 °C: for ambroxol pKa,1T=8.05 (6) and 8.25 (4), log β21T=11.67 (6) and 11.83 (8), for antazoline pKa,1T=7.79 (2) and 7.83 (6), pKa,2T=9.74 (3) and 9.55 (2), for naphazoline pKa,1T=10.81 (1) and 10.63 (1), for oxymethazoline pKa,1T=10.62 (2) and 10.77 (7), pKa,2T=12.03(3) and 11.82 (4) and for ranitidine pKa,1T=1.89 (1) and 1.77 (1). Goodness-of-fit tests for various regression diagnostics enabled the reliability of the parameter estimates to be found. [Copyright &y& Elsevier]

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.