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American Journal of Veterinary Research Feb 2020To examine the effects of imidazoline and nonimidazoline α-adrenergic agents on aggregation of feline platelets.
Effects of imidazoline and nonimidazoline α-adrenoceptor agonists and antagonists, including xylazine, medetomidine, dexmedetomidine, yohimbine, and atipamezole, on aggregation of feline platelets.
OBJECTIVE
To examine the effects of imidazoline and nonimidazoline α-adrenergic agents on aggregation of feline platelets.
SAMPLE
Blood samples from 12 healthy adult cats.
PROCEDURES
In 7 experiments, the effects of 23 imidazoline and nonimidazoline α-adrenoceptor agonists or antagonists on aggregation and antiaggregation of feline platelets were determined via a turbidimetric method. Collagen and ADP were used to initiate aggregation.
RESULTS
Platelet aggregation was not induced by α-adrenoceptor agonists alone. Adrenaline and noradrenaline induced a dose-dependent potentiation of ADP- or collagen-induced aggregation. Oxymetazoline and xylometazoline also induced a small potentiation of ADP-stimulated aggregation, but other α-adrenoceptor agonists did not induce potentiation. The α-adrenoceptor antagonists and certain imidazoline α-adrenergic agents including phentolamine, yohimbine, atipamezole, clonidine, medetomidine, and dexmedetomidine inhibited adrenaline-potentiated aggregation induced by ADP or collagen in a dose-dependent manner. The imidazoline compound antazoline inhibited adrenaline-potentiated aggregation in a dose-dependent manner. Conversely, α-adrenoceptor antagonists and nonimidazoline α-adrenergic agents including xylazine and prazosin were ineffective or less effective for inhibiting adrenaline-potentiated aggregation. Moxonidine also was ineffective for inhibiting adrenaline-potentiated aggregation induced by collagen. Medetomidine and xylazine did not reverse the inhibitory effect of atipamezole and yohimbine on adrenaline-potentiated aggregation.
CONCLUSIONS AND CLINICAL RELEVANCE
Adrenaline-potentiated aggregation of feline platelets may be mediated by α-adrenoceptors, whereas imidazoline agents may inhibit in vitro platelet aggregation via imidazoline receptors. Imidazoline α-adrenergic agents may have clinical use for conditions in which there is platelet reactivity to adrenaline. Xylazine, medetomidine, and dexmedetomidine may be used clinically in cats with minimal concerns for adverse effects on platelet function.
Topics: Adrenergic alpha-Antagonists; Animals; Blood Platelets; Cats; Dexmedetomidine; Imidazoles; Imidazolines; Medetomidine; Xylazine; Yohimbine
PubMed: 31985287
DOI: 10.2460/ajvr.81.2.159 -
International Journal of Molecular... Dec 2020Antazoline (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...
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 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.
Topics: Antazoline; Chromatography, Liquid; Healthy Volunteers; Hepatocytes; Humans; In Vitro Techniques; Tandem Mass Spectrometry
PubMed: 33353167
DOI: 10.3390/ijms21249693 -
Spectrochimica Acta. Part A, Molecular... Apr 2016A comparative study was developed between two classical spectrophotometric methods (dual wavelength method and Vierordt's method) and two recent methods manipulating... (Comparative Study)
Comparative Study
Comparative study between recent methods manipulating ratio spectra and classical methods based on two-wavelength selection for the determination of binary mixture of antazoline hydrochloride and tetryzoline hydrochloride.
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.
Topics: Antazoline; Anti-Allergic Agents; Drug Combinations; Imidazoles; Nasal Decongestants; Quality Control; Spectrophotometry
PubMed: 26836449
DOI: 10.1016/j.saa.2016.01.014 -
Postepy W Kardiologii Interwencyjnej =... Mar 2024Antazoline with propafenone may be an alternative to electrical cardioversion (ECV) in restoring sinus rhythm in patients with atrial fibrillation (AF), including during...
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%]; = 0.01). A similar relationship was demonstrated in patients with persistent AF (13 [59.1%] vs. 3 [12.5%]; = 0.002). There was no significant difference in the group of patients with paroxysmal AF (18 (85.6%) vs. 17 (77.3%); = 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.
PubMed: 38616946
DOI: 10.5114/aic.2024.136392 -
Luminescence : the Journal of... Mar 2024A novel spectrofluorimetric method has been developed for determination of antazoline (ANT) and tetryzoline (TET) in their pharmaceutical formulation. A combined...
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.
Topics: Antazoline; Spectrometry, Fluorescence; Imidazoles
PubMed: 38516711
DOI: 10.1002/bio.4728 -
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 -
Kardiologia Polska 2023Data 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...
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.
Topics: Female; Humans; Male; Amiodarone; Antazoline; Anti-Arrhythmia Agents; Atrial Fibrillation; Electric Countershock; Propafenone; Treatment Outcome; Sex Factors; Multicenter Studies as Topic
PubMed: 37997824
DOI: 10.33963/v.kp.97392 -
BMC Medical Genomics May 2021This study aimed to determine and verify the prognostic value and potential functional mechanism of signal recognition particle 14 (SRP14) in acute myeloid leukemia...
BACKGROUND
This study aimed to determine and verify the prognostic value and potential functional mechanism of signal recognition particle 14 (SRP14) in acute myeloid leukemia (AML) using a genome-wide expression profile dataset.
METHODS
We obtained an AML genome-wide expression profile dataset and clinical prognostic data from The Cancer Genome Atlas (TCGA) and GSE12417 databases, and explored the prognostic value and functional mechanism of SRP14 in AML using survival analysis and various online tools.
RESULTS
Survival analysis showed that AML patients with high SRP14 expression had poorer overall survival than patients with low SRP14 expression. Time-dependent receiver operating characteristic curves indicated that SRP14 had good accuracy for predicting the prognosis in patients with AML. Genome-wide co-expression analysis suggested that SRP14 may play a role in AML by participating in the regulation of biological processes and signaling pathways, such as cell cycle, cell adhesion, mitogen-activated protein kinase, tumor necrosis factor, T cell receptor, DNA damage response, and nuclear factor-kappa B (NF-κB) signaling. Gene set enrichment analysis indicated that SRP14 was significantly enriched in biological processes and signaling pathways including regulation of hematopoietic progenitor cell differentiation and stem cell differentiation, intrinsic apoptotic signaling pathway by p53 class mediator, interleukin-1, T cell mediated cytotoxicity, and NF-κB-inducing kinase/NF-κB signaling. Using the TCGA AML dataset, we also identified four drugs (phenazone, benzydamine, cinnarizine, antazoline) that may serve as SRP14-targeted drugs in AML.
CONCLUSION
The current results revealed that high SRP14 expression was significantly related to a poor prognosis and may serve as a prognostic biomarker in patients with AML.
Topics: Signal Recognition Particle
PubMed: 33985510
DOI: 10.1186/s12920-021-00975-2 -
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 -
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