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British Journal of Pharmacology Sep 19711. The intravenous injection of isoprenaline, orciprenaline, salbutamol and isoetharine increased heart rate in anaesthetized dogs. Log dose-response curves obtained... (Comparative Study)
Comparative Study
1. The intravenous injection of isoprenaline, orciprenaline, salbutamol and isoetharine increased heart rate in anaesthetized dogs. Log dose-response curves obtained with a series of doses of salbutamol and isoetharine were flatter than those for isoprenaline and orciprenaline. The order of activity of the drugs in increasing heart rate was isoprenaline, orciprenaline, and salbutamol=isoetharine.2. The injection into the external iliac artery of isoprenaline, orciprenaline, salbutamol and isoetharine produced dose dependent increases in femoral blood flow. Log dose-response curves for all drugs were parallel. The order of activity of the drugs was isoprenaline, salbutamol=isoetharine and orciprenaline.3. Salbutamol and isoetharine were less active than orciprenaline in increasing heart rate but more active in increasing femoral blood flow.4. These observations indicate that salbutamol and isoetharine have a greater effect on beta(2) than on beta(1)-adrenoceptors in the cardiovascular system.
Topics: Amino Alcohols; Animals; Blood Flow Velocity; Blood Pressure; Cardiovascular System; Catechols; Dogs; Femoral Artery; Heart Rate; Iliac Artery; Injections, Intravenous; Isoproterenol; Metaproterenol; Receptors, Adrenergic; Sympathomimetics
PubMed: 5136459
DOI: 10.1111/j.1476-5381.1971.tb07153.x -
Journal of Clinical Pharmacology 1983The bronchodilator effect of fenoterol hydrobromide (0.5, 1.25, and 2.5 mg) was compared with either isoproterenol (2.8 mg) or isoetharine (5 mg) with phenylephrine... (Clinical Trial)
Clinical Trial Comparative Study
The bronchodilator effect of fenoterol hydrobromide (0.5, 1.25, and 2.5 mg) was compared with either isoproterenol (2.8 mg) or isoetharine (5 mg) with phenylephrine (1.25 mg) in a double-blind placebo-controlled study. When delivered by an intermittent positive-pressure breathing device to 24 nonsmoking young adult asthmatic subjects, fenoterol produced significant improvement in forced expiratory volume at 1 second (FEV1), in maximum midexpiratory flow (FEF25-75%), and in forced expiratory flow at 25 per cent of vital capacity (FEF25%) for 6 to 8 hours, whereas isoproterenol and isoetharine with phenylephrine produced improvement for 1 and 2 hours, respectively. The lowest dosage of fenoterol was as effective as the highest but had fewer adverse effects.
Topics: Adolescent; Adult; Aerosols; Amino Alcohols; Asthma; Child; Child, Preschool; Ethanolamines; Female; Fenoterol; Forced Expiratory Volume; Humans; Infant; Isoetharine; Isoproterenol; Male; Maximal Expiratory Flow Rate; Phenylephrine
PubMed: 6853746
DOI: 10.1002/j.1552-4604.1983.tb02708.x -
Journal of Enzyme Inhibition and... Dec 2017We investigated the influence of bronchodilating β2-agonists on the activity of human acetylcholinesterase (AChE) and usual, atypical and fluoride-resistant...
We investigated the influence of bronchodilating β2-agonists on the activity of human acetylcholinesterase (AChE) and usual, atypical and fluoride-resistant butyrylcholinesterase (BChE). We determined the inhibition potency of racemate and enantiomers of fenoterol as a resorcinol derivative, isoetharine and epinephrine as catechol derivatives and salbutamol and salmeterol as saligenin derivatives. All of the tested compounds reversibly inhibited cholinesterases with K constants ranging from 9.4 μM to 6.4 mM and had the highest inhibition potency towards usual BChE, but generally none of the cholinesterases displayed any stereoselectivity. Kinetic and docking results revealed that the inhibition potency of the studied compounds could be related to the size of the hydroxyaminoethyl chain on the benzene ring. The additional π-π interaction of salmeterol's benzene ring and Trp286 and hydrogen bond with His447 probably enhanced inhibition by salmeterol which was singled out as the most potent inhibitor of all the cholinesterases.
Topics: Adrenergic beta-2 Receptor Agonists; Benzyl Alcohols; Catechols; Cholinesterase Inhibitors; Cholinesterases; Dose-Response Relationship, Drug; Humans; Molecular Structure; Receptors, Adrenergic, beta-2; Resorcinols; Structure-Activity Relationship
PubMed: 28573890
DOI: 10.1080/14756366.2017.1326109 -
The Cochrane Database of Systematic... 2001Inhaled short acting beta2 adrenergic agonists and ipratropium bromide are both used in the treatment of acute exacerbations of chronic obstructive pulmonary disease. (Review)
Review
BACKGROUND
Inhaled short acting beta2 adrenergic agonists and ipratropium bromide are both used in the treatment of acute exacerbations of chronic obstructive pulmonary disease.
OBJECTIVES
In patients with acute exacerbations of COPD to: 1. To assess the efficacy of short-acting beta-2 agonists against placebo; 2. Compare the efficacy of short-acting beta-2 agonists and ipratropium.
SEARCH STRATEGY
A comprehensive search of the literature was carried out of EMBASE, MEDLINE, CINAHL and the Cochrane COPD trials register was carried out using the terms: bronchodilator* OR albuterol OR metaproterenol OR terbutaline OR isoetharine OR pirbuterol OR salbutamol OR beta-2 agonist.
SELECTION CRITERIA
All trials that appeared to be relevant were assessed by two reviewers who independently selected trials for inclusion. Differences were resolved by consensus.
DATA COLLECTION AND ANALYSIS
All trials that appeared to be relevant were assessed by two reviewers who independently selected trials for inclusion. Differences were resolved by consensus. References listed in each included trial were searched for additional trial reports. Trials were combined using Review Manager using a fixed effects model. The size of the treatment effects were tested for heterogeneity.
MAIN RESULTS
We identified no placebo-controlled comparisons of beta-2 agonists. Three studies permitted comparison of ipratropium to an inhaled beta-2 agonist. These studies included a total of 103 patients. The beta2-agonists used were: fenoterol and metaproterenol. One study was a parallel group trial of regular therapy for seven days. The other two were cross over studies of single dose treatments, with efficacy measured 90 min post dose. There was no washout period between treatments. Both treatments produced an improvement in forced expiratory volume (FEV1) after 90 min in the range 150-250 ml. The was no difference between treatments, mean difference in FEV1 10 ml; 95% CI -220, 230 ml. In one small crossover study (n=10) there was a significant improvement in arterial PaO2 after 30 minutes with ipratropium (+5.8 mm Hg +/- 3.0 (SEM)) compared to metaproterenol (-6.2 +/- 1.2 mm Hg), but this was not significant at 90 min. There were no data concerning respiratory symptoms. The crossover studies showed no evidence of an additive effect of the two treatments, although they were not designed specifically to test this.
REVIEWER'S CONCLUSIONS
There are few controlled trial data concerning the use of inhaled beta2-agonist agents in acute exacerbations of COPD and none that have compared these agents directly with placebo. None of the studies used the more modern beta2-agonists used most widely in this setting (salbutamol and terbutaline). Beta2-agonists and ipratropium both produce small improvements in FEV1, but beta2-agonists may worsen PaO2 for a period. We could not draw conclusions concerning possible additive effects.
Topics: Administration, Inhalation; Adrenergic beta-Agonists; Bronchodilator Agents; Humans; Ipratropium; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic
PubMed: 11406052
DOI: 10.1002/14651858.CD002984 -
Journal of Applied Physiology... Feb 1997In anesthetized sheep, we measured bronchial blood flow (Qbr) by an ultrasonic flow probe to investigate the interaction between inhaled nitric oxide (NO; 100...
In anesthetized sheep, we measured bronchial blood flow (Qbr) by an ultrasonic flow probe to investigate the interaction between inhaled nitric oxide (NO; 100 parts/million) given for 5 min and 5 ml of aerosolized isoetharine (1.49 x 10(-2) M concentration). NO and isoetharine increased Qbr from 26.5 +/- 6.5 to 39.1 (SE) +/- 10.6 and 39.7 +/- 10.7 ml/min, respectively (n = 5). Administration of NO immediately after isoetharine further increased Qbr to 57.3 +/- 15.1 ml/min. NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME; 30 mg/kg, in 20 ml saline given i.v.) decreased Qbr to 14.6 +/- 2.6 ml/min. NO given three times alternately with isoetharine progressively increased Qbr from 14.6 +/- 2.6 to 74.3 +/- 17.0 ml/min, suggesting that NO and isoetharine potentiate vasodilator effects of each other. In three other sheep, after L-NAME three sequential doses of isoetharine increased Qbr from 10.2 +/- 3.4 to 11.5 +/- 5.7, 11.7 +/- 4.7, and 13.3 +/- 5.7 ml/min, respectively, indicating that effects of isoetharine are predominantly mediated through synthesis of NO. When this was followed by three sequential administrations of NO, Qbr increased by 146, 172, and 185%, respectively. Thus in the bronchial circulation, there seems to be a close interaction between adenosine 3',5'-cyclic monophosphate- and guanosine 3',5'-cyclic monophosphate-mediated vasodilation.
Topics: Animals; Bronchial Arteries; Isoetharine; Nitric Oxide; Sheep; Vasodilation
PubMed: 9049753
DOI: 10.1152/jappl.1997.82.2.686 -
Saudi Journal of Biological Sciences May 2022Hertwig's Εpithelial Root Sheath (HΕRS) has a major function in the developing tooth roots. Earlier research revealed that it undergoes epithelial-mesenchymal...
Gene and protein interaction network analysis in the epithelial-mesenchymal transition of Hertwig's Epithelial Root Sheath reveals periodontal regenerative drug targets - An in silico study.
BACKGROUND AND AIM
Hertwig's Εpithelial Root Sheath (HΕRS) has a major function in the developing tooth roots. Earlier research revealed that it undergoes epithelial-mesenchymal transition, a vital process for the morphogenesis and complete development of the tooth and its surrounding periodontium. Few studies have demonstrated the role of HERS in cementogenesis through ΕMΤ. The background of this in-silico system biology approach is to find a hub protein and gene involved in the EMT of HERS that may uncover novel insights in periodontal regenerative drug targets.
MATERIALS AND METHODS
The protein and gene list involved in epithelial-mesenchymal transition were obtained from literature sources. The protein interaction was constructed using STRING software and the protein interaction network was analyzed. Molecular docking simulation checks the binding energy and stability of protein-ligand complex.
RESULTS
Results revealed the hub gene to be DYRK1A(Hepcidin), and the ligand was identified as isoetharine. SΤRIΝG results showed a confidence cutoff of 0.9 in sensitivity analysis with a condensed protein interaction network. Overall, 98 nodes from 163 nodes of expected edges were found with an average node degree of 11.9. Docking results show binding energy of -4.70, and simulation results show an RMSD value of 5.6 Å at 50 ns.
CONCLUSION
Isoetharine could be a potential drug for periodontal regeneration.
PubMed: 35844389
DOI: 10.1016/j.sjbs.2022.03.007 -
Thorax Nov 1968The actions of the following pressurized bronchodilators were compared by administration to 24 asthmatics: (1) Medihaler Iso Forte, (2) Alupent, (3) Medihaler-duo, (4)... (Comparative Study)
Comparative Study
The actions of the following pressurized bronchodilators were compared by administration to 24 asthmatics: (1) Medihaler Iso Forte, (2) Alupent, (3) Medihaler-duo, (4) Bronchilator, and (5) Prenomiser Plus. These contained one or more of the following: isoprenaline, orciprenaline, isoetharine, phenylephrine, atropine methonitrate, and thenyldiamine. The dose was a single discharge from the container. The response was assessed by calculating the mean percentage change in F.E.V. at intervals after inhalation. The mean peak rises were respectively (1) 49·4%, (2) 43·6%, (3) 36·2%, (4) 33·5%, and (5) 23·5%. The amplitude of peak response to isoprenaline was related to the logarithm of the dose. Weight for weight, orciprenaline had a peak bronchodilator activity 41·5% that of isoprenaline and isoetharine 50%. The preparations did not differ significantly in the time taken to reach maximum response, which varied from 5 to 60 minutes; three-quarters of the maxima occurred within 15 minutes. The half-life for Alupent was 2 hours; for Medihaler-duo, which contains 240 μg. of phenylephrine per dose, it was 1¼ hours; for the remaining preparations it was about 1 hour. The decay rate, after the first half-hour, was 6% of the basal F.E.V. per hour for Medihaler-duo; for the other preparations it was 10-12%. In the doses given, Alupent yielded 20% and 30% increases lasting 130 and 67 minutes; after Medihaler Iso Forte these lasted 78 and 46 minutes. Similar comparative experiments, designed to eliminate effects of dosage difference, are desirable. Rebound bronchoconstriction occurred in 23% of 92 experiments. There was no response to propellent alone. The mean percentage change in F.E.V. may not be the best way of expressing results.
Topics: Adult; Aerosols; Aged; Asthma; Atropine; Bronchial Spasm; Bronchodilator Agents; Female; Histamine H1 Antagonists; Humans; Isoproterenol; Male; Metaproterenol; Middle Aged; Phenylephrine
PubMed: 4388005
DOI: 10.1136/thx.23.6.590 -
Biochemical Pharmacology Nov 2012Catecholic drugs had been reported to be metabolized through conjugation reactions, particularly methylation and sulfation. Whether and how these two Phase II...
Catecholic drugs had been reported to be metabolized through conjugation reactions, particularly methylation and sulfation. Whether and how these two Phase II conjugation reactions may occur in a concerted manner, however, remained unclear. The current study was designed to investigate the methylation and/or sulfation of five catecholic drugs. Analysis of the spent media of HepG2 cells metabolically labeled with [(35)S]sulfate in the presence of individual catecholic drugs revealed the presence of two [(35)S]sulfated metabolites for dopamine, epinephrine, isoproterenol, and isoetharine, but only one [(35)S]sulfated metabolite for apomorphine. Further analyses using tropolone, a catechol O-methyltransferase (COMT) inhibitor, indicated that one of the two [(35)S]sulfated metabolites of dopamine, epinephrine, isoproterenol, and isoetharine was a doubly conjugated (methylated and sulfated) product, since its level decreased proportionately with increasing concentrations of tropolone added to the labeling media. Moreover, while the inhibition of methylation resulted in a decrease of the total amount of [(35)S]sulfated metabolites, sulfation appeared to be capable of compensating the suppressed methylation in the metabolism of these four catecholic drugs. A two-stage enzymatic assay showed the sequential methylation and sulfation of dopamine, epinephrine, isoproterenol, and isoetharine mediated by, respectively, the COMT and the cytosolic sulfotransferase SULT1A3. Collectively, the results from the present study implied the concerted actions of the COMT and SULT1A3 in the metabolism of catecholic drugs.
Topics: Arylsulfotransferase; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Catechols; Hep G2 Cells; Humans; Methylation; Solubility; Sulfotransferases; Sulfuric Acid Esters; Tropolone
PubMed: 22917559
DOI: 10.1016/j.bcp.2012.08.009 -
Structure (London, England : 1993) Mar 2020G-protein-coupled receptors (GPCRs) mediate a wide range of human physiological functions by transducing extracellular ligand binding events into intracellular...
G-protein-coupled receptors (GPCRs) mediate a wide range of human physiological functions by transducing extracellular ligand binding events into intracellular responses. GPCRs can activate parallel, independent signaling pathways mediated by G proteins or β-arrestins. Whereas "balanced" agonists activate both pathways equally, "biased" agonists dominantly activate one pathway, which is of interest for designing GPCR-targeting drugs because it may mitigate undesirable side effects. Previous studies demonstrated that β-arrestin activation is associated with transmembrane helix VII (TM VII) of GPCRs. Here, single-molecule fluorescence spectroscopy with the β-adrenergic receptor (βAR) in the ligand-free state showed that TM VII spontaneously fluctuates between one inactive and one active-like conformation. The presence of the β-arrestin-biased agonist isoetharine prolongs the dwell time of TM VII in the active-like conformation compared with the balanced agonist formoterol, suggesting that ligands can induce signaling bias by modulating the kinetics of receptor conformational exchange.
Topics: Binding Sites; Humans; Isoetharine; Kinetics; Models, Molecular; Protein Binding; Protein Conformation; Protein Domains; Protein Structure, Secondary; Receptors, Adrenergic, beta-2; Signal Transduction; Single Molecule Imaging; Spectrometry, Fluorescence; beta-Arrestins
PubMed: 31978323
DOI: 10.1016/j.str.2020.01.001