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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 -
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 -
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 -
Cardiology Journal 2024
Comparative Study
Topics: Humans; Anti-Arrhythmia Agents; Emergency Service, Hospital; Flecainide; Amiodarone; Heart Rate; Male; Propafenone; Treatment Outcome; Female; Antazoline; Aged; Middle Aged; Atrial Fibrillation
PubMed: 38771221
DOI: 10.5603/cj.96610 -
Journal of Pharmaceutical and... Aug 20212-Imidazoline drugs are used in a variety of applications, such as the treatment of hypertension and opioid withdrawal. It is known these drugs bind to serum proteins...
2-Imidazoline drugs are used in a variety of applications, such as the treatment of hypertension and opioid withdrawal. It is known these drugs bind to serum proteins and have significant variations within this class of compounds in the overall level of this binding. However, little specific information is available on the interactions of these compounds with the two major transport proteins for many drugs, human serum albumin (HSA) and alpha-acid glycoprotein (AGP). This study examined binding by 2-imidazolines to these proteins by using 25 mm × 2.1 mm i.d. high-performance affinity microcolumns that contained HSA or AGP. The drugs that were examined were antazoline, clonidine, dexmedetomidine, lofexidine, moxonidine, phentolamine, and tizanidine, which represented a wide range of structures and pharmaceutical applications. The major metabolite of lofexidine, N-(2-aminoethyl)-2-(2,6-dichlorophenoxy) propenamide (LADP), was also examined. All these 2-imidazolines were found to have weak-to-moderate binding to HSA, with global affinities that ranged from 1.62 × 10 to 1.07 × 10 M at pH 7.4 and 37 °C. These compounds had stronger binding with AGP, with global affinities constants ranging from 3.80 × 10 to 1.85 × 10 M. No stereoselectivity was observed by HSA for the enantiomers of dexmedetomidine, lofexidine, or LADP. However, AGP did show some stereoselectivity for lofexidine and LADP but not for dexmedetomidine. These results provide a better understanding of interactions of 2-imidazoline with HSA vs AGP in the circulation and of how this binding can change between drugs within this class of compounds.
Topics: Chromatography, Affinity; Humans; Imidazoles; Imidazolines; Orosomucoid; Protein Binding; Serum Albumin, Human
PubMed: 34022667
DOI: 10.1016/j.jpba.2021.114135 -
Annals of Emergency Medicine Jul 2020We conduct a systematic review and Bayesian network meta-analysis to indirectly compare and rank antidysrhythmic drugs for pharmacologic cardioversion of recent-onset...
STUDY OBJECTIVE
We conduct a systematic review and Bayesian network meta-analysis to indirectly compare and rank antidysrhythmic drugs for pharmacologic cardioversion of recent-onset atrial fibrillation and atrial flutter in the emergency department (ED).
METHODS
We searched MEDLINE, EMBASE, and Web of Science from inception to March 2019, limited to human subjects and English language. We also searched for unpublished data. We limited studies to randomized controlled trials that enrolled adult patients with recent-onset atrial fibrillation or atrial flutter and compared antidysrhythmic agents, placebo, or control. We determined these outcomes before data extraction: rate of conversion to sinus rhythm within 4 hours, time to cardioversion, rate of significant adverse events, and rate of thromboembolism within 30 days. We extracted data according to Preferred Reporting Items for Systematic Reviews and Meta-analyses network meta-analysis and appraised selected trials with the Cochrane review handbook.
RESULTS
The systematic review initially identified 640 studies; 19 met inclusion criteria. Eighteen trials that randomized 2,069 atrial fibrillation patients provided data for atrial fibrillation conversion rate outcome. Bayesian network meta-analysis using a random-effects model demonstrated that antazoline (odds ratio [OR] 24.9; 95% credible interval [CrI] 7.4 to 107.8), tedisamil (OR 12.0; 95% CrI 4.3 to 43.8), vernakalant (OR 7.5; 95% CrI 3.1 to 18.6), propafenone (OR 6.8; 95% CrI 3.6 to 13.8), flecainide (OR 6.1; 95% CrI 2.9 to 13.2), and ibutilide (OR 4.1; 95% CrI 1.8 to 9.6) were associated with increased likelihood of conversion within 4 hours compared with placebo or control. Overall quality was low, and the network exhibited inconsistency.
CONCLUSION
For pharmacologic cardioversion of recent-onset atrial fibrillation within a 4-hour ED visit, there is insufficient evidence to determine which treatment is superior. Several agents are associated with increased likelihood of conversion within 4 hours compared with placebo or control. Limited data preclude any recommendation for cardioversion of recent-onset atrial flutter. Further high-quality study is necessary.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Bayes Theorem; Emergency Service, Hospital; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32173135
DOI: 10.1016/j.annemergmed.2020.01.013