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British Journal of Clinical Pharmacology Jul 2019Antazoline is a first-generation antihistaminic drug used primarily in eye drop formulations. When administered intravenously, antazoline displays antiarrhythmic...
Intravenous antazoline, a first-generation antihistaminic drug with antiarrhythmic properties, is a suitable agent for pharmacological cardioversion of atrial fibrillation induced during pulmonary vein isolation due to the lack of influence on atrio-venous conduction and high clinical effectiveness...
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 CHA DS -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.
Topics: Administration, Intravenous; Aged; Antazoline; Anti-Arrhythmia Agents; Atrial Fibrillation; Cryosurgery; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Prospective Studies; Pulmonary Veins
PubMed: 30920001
DOI: 10.1111/bcp.13940 -
Acta Ophthalmologica Aug 2019To investigate whether exposure to antazoline-naphazoline eye drops in the first trimester of pregnancy was associated with an increased risk of malformations in humans.
PURPOSE
To investigate whether exposure to antazoline-naphazoline eye drops in the first trimester of pregnancy was associated with an increased risk of malformations in humans.
METHODS
All women giving live birth between 1997 and 2011 in Denmark were included in this nationwide cohort study. All women redeeming at least one prescription of antazoline-naphazoline eye drops during the first 84 days of pregnancy were identified. Logistic regression was used to estimate the odds ratios of malformations among exposed offspring compared to non-exposed offspring.
RESULTS
We identified 977 706 births between 1997 and 2011. A total of 3061 women (0.32%) were exposed to antazoline-naphazoline eye drops in the first trimester of pregnancy. The rate of congenital malformations was 3.0% (n = 93) in exposed offspring and 3.5% (n = 33 594) in unexposed offspring. First-trimester exposure to antazoline-naphazoline was not associated with major congenital malformations overall (odds ratio: 0.88, 95% confidence interval: 0.71-1.09) or with any specific major malformation. The number of redeemed prescriptions was unchanged during all trimesters of pregnancy as compared to before and after pregnancy (p < 0.05).
CONCLUSION
Exposure to antazoline-naphazoline eye drops in the first trimester of pregnancy appears not to be associated with increased teratogenic risk.
Topics: Abnormalities, Drug-Induced; Adult; Antazoline; Anti-Allergic Agents; Denmark; Female; Follow-Up Studies; Humans; Incidence; Infant, Newborn; Male; Naphazoline; Nasal Decongestants; Ophthalmic Solutions; Population Surveillance; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Registries; Retrospective Studies; Risk Factors; Young Adult
PubMed: 30479070
DOI: 10.1111/aos.13980 -
Pharmacological Cardioversion With Antazoline in Atrial Fibrillation: The Results of the CANT Study.Journal of the American Heart... Oct 2018Background Antazoline mesylate represents an antihistamine capable of rapid and safe cardioversion of atrial fibrillation, yet evidence concerning its efficacy in... (Observational Study)
Observational Study
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 <45 bpm, hypotension, syncope, or death. The study population (mean age, 65.5±11.9 years; 52.9% females) was characterized by a median atrial fibrillation episode duration of 10 hours. Antazoline, alone or in combination, was administered in 24.2% (n=109) and 40% (n=180), respectively; amiodarone was administered in 46.7% and propafenone in 9.3%, while ≥2 antiarrhythmic drugs were administered in 19.8% of patients. Antazoline had the highest success rate of pharmacological cardioversion among all drugs (85.3%), which was comparable with propafenone (78.6%; relative risk, 1.09, 95% confidence interval, 0.91-1.30; P=0.317) and higher than amiodarone treatment (66.7%; relative risk, 1.28, 95% confidence interval, 1.13-1.45; P<0.001; number needed to treat, 5.4). The rate of cardioversion with antazoline alone was higher than combined amiodarone and/or propafenone (68.1%; relative risk, 1.25; 95% confidence interval, 1.12-1.40, P=0.0001). No safety end points were reported in the antazoline group, while 5 incidents occurred in the non-antazoline cohort ( P=0.075). Conclusions Antazoline represents an efficacious and safe method of pharmacological cardioversion in a real-life setting.
Topics: Aged; Antazoline; Anti-Arrhythmia Agents; Atrial Fibrillation; Drug Therapy, Combination; Female; Histamine H1 Antagonists; Humans; Male; Retrospective Studies; Treatment Outcome
PubMed: 30371270
DOI: 10.1161/JAHA.118.010153 -
Cardiovascular Therapeutics Dec 2018Options for a pharmacological cardioversion (CV) of short-duration atrial fibrillation (AF) in patients with a stable coronary artery disease (CAD) are limited to...
Clinical effectiveness and safety of antazoline-based therapy in patients with stable coronary artery disease undergoing pharmacological cardioversion of short-duration atrial fibrillation in the emergency department.
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.
Topics: Aged; Antazoline; Anti-Arrhythmia Agents; Atrial Fibrillation; Comorbidity; Coronary Artery Disease; Emergency Service, Hospital; Female; Heart Conduction System; Heart Rate; Humans; Male; Medical Records; Middle Aged; Patient Admission; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome
PubMed: 30281920
DOI: 10.1111/1755-5922.12469 -
Bioorganic & Medicinal Chemistry May 2018A series of 1- and 2-naphthyloxy derivatives were synthesized and evaluated for histamine H receptor affinity. Most compounds showed high affinities with K values below...
A series of 1- and 2-naphthyloxy derivatives were synthesized and evaluated for histamine H receptor affinity. Most compounds showed high affinities with K values below 100 nM. The most potent ligand, 1-(5-(naphthalen-1-yloxy)pentyl)azepane (11) displayed high affinity for the histamine H receptor with a K value of 21.9 nM. The antagonist behaviour of 11 was confirmed both in vitro in the cAMP assay (IC = 312 nM) and in vivo in the rat dipsogenia model (ED = 3.68 nM). Moreover, compound 11 showed positive effects on scopolamine induced-memory deficits in mice (at doses of 10 and 15 mg/kg) and an analgesic effect in the formalin test in mice with ED = 30.6 mg/kg (early phase) and ED = 20.8 mg/kg (late phase). Another interesting compound, 1-(5-(Naphthalen-1-yloxy)pentyl)piperidine (13; HR K = 53.9 nM), was accepted for Anticonvulsant Screening Program at the National Institute of Neurological Disorders and Stroke/National Institute of Health (Rockville, USA). The screening was performed in the maximal electroshock seizure (MES), the subcutaneous pentylenetetrazole (scPTZ) and the 6-Hz psychomotor animal models of epilepsy. Neurologic deficit was evaluated by the rotarod test. Compound 13 inhibited convulsions induced by the MES with ED of 19.2 mg/kg (mice, i.p.), 17.8 (rats, i.p.), and 78.1 (rats, p.o.). Moreover, 13 displayed protection against the 6-Hz psychomotor seizures (32 mA) in mice (i.p.) with ED of 33.1 mg/kg and (44 mA) ED of 57.2 mg/kg. Furthermore, compounds 11 and 13 showed in vitro weak influence on viability of tested cell lines (normal HEK293, neuroblastoma IMR-32, hepatoma HEPG2), weak inhibition of CYP3A4 activity, and no mutagenicity. Thus, these compounds may be used as leads in a further search for histamine H receptor ligands with promising in vitro and in vivo activity.
Topics: Analgesics; Animals; Antazoline; Anticonvulsants; Atropine; Azepines; Dose-Response Relationship, Drug; Guinea Pigs; HEK293 Cells; Histamine H3 Antagonists; Humans; Ligands; Male; Mice; Naphthalenes; Piperidines; Rats, Wistar; Receptor, Muscarinic M3; Receptors, Histamine H1; Receptors, Histamine H3
PubMed: 29681486
DOI: 10.1016/j.bmc.2018.04.023 -
Cardiovascular Drugs and Therapy Apr 2018Antazoline is a first-generation antihistaminic agent with additional anticholinergic properties and antiarrhythmic potential. Recent data shows its high effectiveness...
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.
Topics: Action Potentials; Adult; Aged; Antazoline; Anti-Arrhythmia Agents; Atrial Flutter; Catheter Ablation; Dose-Response Relationship, Drug; Female; Heart Atria; Heart Conduction System; Heart Rate; Humans; Male; Middle Aged; Papillary Muscles; Tachycardia, Atrioventricular Nodal Reentry; Treatment Outcome; Young Adult
PubMed: 29623481
DOI: 10.1007/s10557-018-6787-9 -
Antiarrhythmic effect of antazoline in experimental models of acquired short- and long-QT-syndromes.Europace : European Pacing,... Oct 2018Antazoline is a first-generation antihistamine with antiarrhythmic properties. This study examines potential electrophysiological effects of antazoline in...
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.
Topics: Action Potentials; Adrenergic beta-Antagonists; Animals; Antazoline; Anti-Bacterial Agents; Arrhythmias, Cardiac; Disease Models, Animal; Erythromycin; Histamine H1 Antagonists; Isolated Heart Preparation; Long QT Syndrome; Membrane Transport Modulators; Pinacidil; Rabbits; Refractory Period, Electrophysiological; Sotalol; Torsades de Pointes; Ventricular Fibrillation
PubMed: 29377987
DOI: 10.1093/europace/eux383 -
Acta Chimica Slovenica Jun 2017In the present study, a newly developed method based on ultrahigh performance liquid chromatography (UHPLC) was optimized for the simultaneous determination of...
In the present study, a newly developed method based on ultrahigh performance liquid chromatography (UHPLC) was optimized for the simultaneous determination of antazoline hydrochloride (ANZ) and naphazoline hydrochloride (NFZ) in ophthalmic formulations. Isocratic separation of ANZ and NFZ was performed at 40 °C with an ACE Excel 2 C18-PFP column (2 μm, 2.1 × 100 mm) at a flow rate of 0.6 mL min-1 whereas the mobile phase consisted of acetonitrile/phosphate buffer (60:40, v/v, pH 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 per sample was 4.5 min with retention time of 0.92 and 1.86 min for NFZ and ANZ, respectively. The calibration curve was linear from 0.500-100 μg mL-1 for ANZ and NFZ with a correlation coefficient ≥ 0.9981 while repeatability and reproducibility (expressed as relative standard deviation) were lower than 1.28 and 2.14%, respectively. In comparison with high-performance liquid chromatography (HPLC), the developed UHPLC method had remarkable advantages over HPLC as the run time was significantly reduced by 3.4-fold with a 5-fold decreased solvent consumption. Forced degradation studies indicated a complete separation of the analytes in the presence of their degradation products providing high degree of method specificity. The proposed UHPLC method was demonstrated to be simple and rapid for the determination of ANZ and NFZ in commercially available ophthalmic formulations providing recoveries between 99.6 and 100.4%.
PubMed: 28621384
DOI: 10.17344/acsi.2017.3166 -
Annals of Noninvasive Electrocardiology... Sep 2017Antazoline is an old antihistaminic and new antiarrhythmic agent with unknown mechanisms of action which recently has been shown to effectively terminate atrial...
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.
Topics: Adult; Antazoline; Anti-Arrhythmia Agents; Blood Pressure; Electrocardiography; Female; Heart Rate; Hemodynamics; Histamine H1 Antagonists; Humans; Male; Reference Values; Stroke Volume
PubMed: 28236352
DOI: 10.1111/anec.12441 -
Cardiovascular Therapeutics Apr 2017The antihistaminic antazoline (ANT) was reported to be highly effective and safe for rapid conversion of atrial fibrillation (AF). We therefore analyzed underlying...
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.
Topics: Acetylcholine; Action Potentials; Animals; Antazoline; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiac Pacing, Artificial; Dose-Response Relationship, Drug; Drug Discovery; Electrocardiography; Electrophysiologic Techniques, Cardiac; Flecainide; Heart Rate; Histamine H1 Antagonists; Isolated Heart Preparation; Isoproterenol; Rabbits; Refractory Period, Electrophysiological; Time Factors
PubMed: 28039911
DOI: 10.1111/1755-5922.12244