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British Journal of Pharmacology Jun 19961. The effects of beta-adrenoceptor antagonists including (-)- and (+)-propranolol, (-)- and (+)-penbutolol, timolol, pindolol, atenolol, acebutolol and practolol on the...
1. The effects of beta-adrenoceptor antagonists including (-)- and (+)-propranolol, (-)- and (+)-penbutolol, timolol, pindolol, atenolol, acebutolol and practolol on the Ca(2+)-overload induced by lysophosphatidylcholine (LPC) were examined in isolated cardiomyocytes of the rat. 2. Fura-2 was used for measurement of the intracellular calcium concentration ([Ca2+]i). LPC (15 microM) produced a rapid increase in [Ca2+]i from 72 +/- 5 to 3042 +/- 431 nM which coincided with a decrease in the percentage of rod-shaped cells from 69 +/- 2 to 5 +/- 2%. 3. Preincubation with (-)-propranolol (20 microM), (+)-propranolol (50 microM), or (-)- or (+)-penbutolol (20 microM), the lipophilicity of which is higher than other beta-adrenoceptor antagonists, significantly inhibited both the increase in [Ca2+]i and the cell-shape change induced by 15 microM LPC. The inhibitory effects of the four drugs on the LPC-induced increase in [Ca2+]i and cell-shape change were concentration-dependent. The IC50S of (-)-propranolol, (+)-propranolol, (-)- and (+)-penbutolol for the increase in [Ca2+]i were 1.28, 10.50, 0.67 and 0.76 microM, respectively. 4. Pretreatment with pindolol, timolol, acebutolol, practolol, atenolol or lignocaine did not inhibit the increase in [Ca2+]i and the morphological change induced by LPC. 5. LPC markedly increased the release of creatine phosphokinase from 9 +/- 1 to 45 +/- 2% which could be significantly reduced by (-)- or (+)-propranolol but not by acebutolol or timolol. 6. The protective effects of (-)- and (+)-propranolol, (-)- and (+)-penbutolol against the Ca(2+)-overload induced by LPC were not associated with the beta-adrenoceptor antagonistic action, but probably with an unknown action which is related to the preservation of membrane integrity. Further studies are necessary to clarify the exact mechanisms of the protective action of these beta-adrenoceptor antagonists against the Ca(2+)-overload induced by LPC.
Topics: Adrenergic beta-Antagonists; Animals; Calcium; Cell Size; Chelating Agents; Creatine Kinase; Fura-2; Heart; Lysophosphatidylcholines; Male; Myocardium; Rats; Rats, Sprague-Dawley
PubMed: 8799555
DOI: 10.1111/j.1476-5381.1996.tb15479.x -
British Journal of Pharmacology Feb 1980The bronchoconstrictor and beta-adrenoceptor blocking activity of (+/-)-propranolol, acebutolol and two of its analogues were compared in a group of littermate rats.... (Comparative Study)
Comparative Study
The bronchoconstrictor and beta-adrenoceptor blocking activity of (+/-)-propranolol, acebutolol and two of its analogues were compared in a group of littermate rats. Whilst the analogues of acebutolol had similar bronchoconstrictor potency to propranolol, acebutolol had considerably less activity. No correlation could be found between the degree of bronchoconstriction produced by the four drugs and their beta-adrenoceptor blocking activity in the airway smooth muscle. Acebutolol and its analogues show a wide properties could be related to the production of bronchospasm.
Topics: Acebutolol; Adrenergic beta-Antagonists; Airway Resistance; Animals; Bronchi; Guinea Pigs; Heart Rate; Isoproterenol; Propranolol; Rats
PubMed: 6101978
DOI: 10.1111/j.1476-5381.1980.tb10407.x -
Medicine Jan 2016Smith-Magenis syndrome (SMS0) is a complex and rare genetic multisystem disorder characterized by a variable pattern of cognitive deficits accompanied by a1 distinctive...
Smith-Magenis syndrome (SMS0) is a complex and rare genetic multisystem disorder characterized by a variable pattern of cognitive deficits accompanied by a1 distinctive behavioral phenotype. SMS is characterized by subtle facial dysmorphology, short stature, sleep disturbances, and neurobehavioral abnormalities. Little is known about the manifestation of his unique case among Arab population and its strategic treatment.This study comes to present a case of SMS in an Arab newborn male who was born in spontaneous delivery on June 29, 2015, with tachypnea, tracheomalacia, and mild hypotonia. The newborn was admitted on the Neonatal Intensive Care Unit (NICU), and various laboratory examinations and clinical examinations were performed.Throughout his hospitalization, feeding difficulties appeared and thus a peripheral venous catheter was inserted in the left leg.After 22 days of follow-up and hospitalizations, the patient status improved and he was discharged with recommendations to be in follow up in pediatric outpatient clinic.However, notwithstanding the different investigations, intermittent tachypnea continued at a rate of 72 to 77 breaths/min. Search for diagnosis begin intensively owing to persistence of tachypnia, mild hypotonia, feeding difficulties, sleep disturbances, and mild dysmorphic facial features. Suspicions of genetic abnormalities were considered and blood samples were sent for chromosome analysis and for fluorescent in situ hybridization (FISH) testing.The genetic results revealed the following: cytogenetic findings: 46, XY, del(17)(p11.2) and the FISH results: del(17)(p11.2p11.2) (D17S29). The chromosome diagnosis revealed an interstitial deletion of 17p11.2 and the diagnosis of the SMS was confirmed.Accurate clinical diagnosis, therapeutic assessments and a holistic management plans, including multidiscipline therapeutic strategies, periodic neuro-developmental assessments, and an early intervention programs, are recommended.However, cytogenetic analysis or FISH using an RAI1-specific probe is the most frequently used technique for DS. Sleep and behavioral disturbances treatment include a combination of the daytime dose of acebutolol with an evening oral dose of melatonin. Melatonin as chronobiotic, antioxidant, and analgesic agent showed to be effective in different primary sleep disorders and in those associated with neurobehavioral disorders. Based on the beneficial effect of melatonin, it will be useful to use serum levels of melatonin as a follow-up test.
Topics: Acebutolol; Adrenergic beta-1 Receptor Antagonists; Antioxidants; Arabs; Chromosome Deletion; Drug Combinations; Humans; In Situ Hybridization, Fluorescence; Infant, Newborn; Israel; Male; Melatonin; Phenotype; Residence Characteristics; Smith-Magenis Syndrome
PubMed: 26817868
DOI: 10.1097/MD.0000000000002362 -
Journal of Pharmaceutical Sciences Jul 2009Gastrointestinal absorption of several beta-blockers is inhibited by citrus juices, although molecular mechanism(s) lying on their small intestinal absorption has not...
Gastrointestinal absorption of several beta-blockers is inhibited by citrus juices, although molecular mechanism(s) lying on their small intestinal absorption has not yet been identified. Here, we attempted to demonstrate involvement of both influx and efflux transporters in vivo in gastrointestinal absorption of celiprolol in mice. Plasma concentration of celiprolol (3 mg/kg) after oral administration was mostly under the limit of quantification in wild mice, whereas that in mdr1a/b knockout (mdr1a/b(-/-)) mice was much more obvious, indicating P-glycoprotein-mediated efflux. Then, the oral absorption of celiprolol in mdr1a/b(-/-) mice was further examined to investigate influx transport mechanism with avoiding effect of P-glycoprotein. Coadministration of bromosulfophthalein (BSP), an inhibitor of various influx transporters including organic anion transporting polypeptide (OATP) reduced plasma celiprolol concentration. Inhibition by BSP of celiprolol uptake from apical membranes was confirmed in Ussing-type chamber of small intestinal tissues. Uptake of celiprolol by human small intestinal transporter OATP-A/1A2 was also confirmed in Xenopus Laevis oocytes. Interestingly, OATP-A/1A2 accepts various beta-blockers including acebutolol, atenolol and sotalol, oral absorption of which is inhibited by coadministration of citrus juice or telithromycin in human. Taken together, these findings have suggested fundamental role of influx transport system(s) in oral absorption of celiprolol.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Administration, Oral; Adrenergic beta-Antagonists; Animals; Celiprolol; Humans; Intestinal Absorption; Intestine, Small; Male; Mice; Mice, Knockout; Oocytes; Organic Anion Transporters; Sulfobromophthalein; Transfection; Xenopus laevis
PubMed: 19067419
DOI: 10.1002/jps.21618 -
British Journal of Clinical Pharmacology 19821 In 46 patients (16 female and 30 male), aged between 18 and 73 years and effect of acute beta-adrenoceptor blockade with i.v. pindolol, acebutolol and atenolol has...
1 In 46 patients (16 female and 30 male), aged between 18 and 73 years and effect of acute beta-adrenoceptor blockade with i.v. pindolol, acebutolol and atenolol has been studied at rest and during ergometric exercise, during routine intracardiac His bundle investigations. 2 At rest the functional parameters of the sinus node were impaired most markedly by atenolol. A-V nodal conduction was more depressed with acebutolol and atenolol than with pindolol. The His-Purkinje system conduction remained unaffected by all three beta-adrenoceptor blocking agents. 3 During ergometric exercise the depressant action of beta-adrenoceptor blockade on sinus nodal function with lower heart rates and on A-V nodal conduction with slower conduction velocities was equieffective with pindolol, acebutolol and atenolol. His-Purkinje system conduction again remained unchanged with one exception that after administration of pindolol, conduction rate during exercise was faster than before beta-adrenoceptor blockade. 4 It may be concluded that, in patients with low heart rates, an antagonist such as pindolol with relatively pronounced intrinsic sympathomimetic activity can be considered to be the drug of choice. In contrast, patients with higher heart rates at rest should be treated with a cardioselective betablocker without ISA. Patients with overt Sick Sinus Syndrome should not be given beta-adrenoceptor blockers at all. 5 Physical activity may change (improve or impair) the antiarrhythmic potency of beta-adrenoceptor blockers used in the treatment of supraventricular tachycardias or tachyarrhythmias.
Topics: Acebutolol; Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Atenolol; Electrophysiology; Female; Heart; Heart Conduction System; Heart Rate; Humans; Male; Middle Aged; Physical Exertion; Pindolol; Rest; Sympathomimetics
PubMed: 6125178
DOI: 10.1111/j.1365-2125.1982.tb01926.x -
Journal of the American Society of... Apr 2015Some β-blockers are efficiently removed from the circulation by hemodialysis ("high dialyzability") whereas others are not ("low dialyzability"). This characteristic... (Comparative Study)
Comparative Study
Some β-blockers are efficiently removed from the circulation by hemodialysis ("high dialyzability") whereas others are not ("low dialyzability"). This characteristic may influence the effectiveness of the β-blockers among patients receiving long-term hemodialysis. To determine whether new use of a high-dialyzability β-blocker compared with a low-dialyzability β-blocker associates with a higher rate of mortality in patients older than age 66 years receiving long-term hemodialysis, we conducted a propensity-matched population-based retrospective cohort study using the linked healthcare databases of Ontario, Canada. The high-dialyzability group (n=3294) included patients initiating atenolol, acebutolol, or metoprolol. The low-dialyzability group (n=3294) included patients initiating bisoprolol or propranolol. Initiation of a high- versus low-dialyzability β-blocker was associated with a higher risk of death in the following 180 days (relative risk, 1.4; 95% confidence interval, 1.1 to 1.8; P<0.01). Supporting this finding, we repeated the primary analysis in a cohort of patients not receiving hemodialysis and found no significant association between dialyzability and the risk of death (relative risk, 1.0; 95% confidence interval, 0.9 to 1.3; P=0.71). β-Blocker exposure was not randomly allocated in this study, so a causal relationship between dialyzability and mortality cannot be determined. However, our findings should raise awareness of this potentially important drug characteristic and prompt further study.
Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Cardiovascular Diseases; Female; Humans; Kidney Failure, Chronic; Male; Ontario; Renal Dialysis; Retrospective Studies
PubMed: 25359874
DOI: 10.1681/ASN.2014040324 -
British Journal of Pharmacology Oct 19801 Atrial and ventricular chronotropic effects of acebutolol, metoprolol and propranolol were studied in conscious dogs with chronic heart-block. Ventricular...
Acebutolol, metoprolol and propranolol in conscious dogs with chronic heart-block: chronotropic effects and relation between depression of ventricular activity and beta-adrenoceptor blocking potency.
1 Atrial and ventricular chronotropic effects of acebutolol, metoprolol and propranolol were studied in conscious dogs with chronic heart-block. Ventricular beta-adrenoceptor blocking activity was assessed for the three dogs against isoprenaline (1 microgram/kg) under the same experimental conditions. 2 Acebutolol and metoprolol significantly increased atrial rate. The effect was proportional to the dose for acebutolol, independent for metoprolol. Propranolol had no significant effect on atrial rate. All three drugs significantly lowered ventricular rate in proportion to the dose. 3 Ventricular beta-blocking potencies of metoprolol and acebutolol were respectively 2 and 3 times weaker than that of propranolol as indicated by ED50 values. 4 The ventricular depressor effect observed was proportional to the degree of ventricular beta-blockade present, although this may not be the only factor involved.
Topics: Acebutolol; Adrenergic beta-Antagonists; Animals; Blood Pressure; Depression, Chemical; Dogs; Female; Heart Block; Heart Rate; Male; Metoprolol; Propranolol
PubMed: 6107135
DOI: 10.1111/j.1476-5381.1980.tb07941.x -
Journal of Medical Genetics Sep 2001Smith-Magenis syndrome (SMS) is a clinically recognisable contiguous gene syndrome ascribed to interstitial deletions of chromosome 17p11.2. Patients have a phase shift...
Smith-Magenis syndrome (SMS) is a clinically recognisable contiguous gene syndrome ascribed to interstitial deletions of chromosome 17p11.2. Patients have a phase shift of their circadian rhythm of melatonin with a paradoxical diurnal secretion of the hormone. Serum melatonin levels and day-night behaviour were studied in nine SMS children (aged 4 to 17 years) given acebutolol, a selective beta(1)-adrenergic antagonist (10 mg/kg early in the morning). Cardiac examination, serum melatonin, motor activity recordings, and sleep diaries were monitored before and after drug administration. The present study shows that a single morning dose of acebutolol suppressed the inappropriate secretion of melatonin in SMS. A significant improvement of inappropriate behaviour with increased concentration, delayed sleep onset, increased hours of sleep, and delayed waking were also noted. These results suggest that beta(1)-adrenergic antagonists help to manage hyperactivity, enhance cognitive performance, and reduce sleep disorders in SMS.
Topics: Acebutolol; Adolescent; Adrenergic beta-Antagonists; Behavior; Child; Child, Preschool; Chromosomes, Human, Pair 17; Chronobiology Disorders; Circadian Rhythm; Cognition; Female; Humans; Hyperkinesis; In Situ Hybridization, Fluorescence; Male; Melatonin; Sleep; Sleep Wake Disorders; Syndrome; Wakefulness
PubMed: 11546826
DOI: 10.1136/jmg.38.9.586 -
British Journal of Pharmacology Sep 19891. Presynaptic beta-adrenoceptor activity was studied in rat isolated atria, previously loaded with [3H]-noradrenaline. The stimulation-induced release of 3H transmitter...
1. Presynaptic beta-adrenoceptor activity was studied in rat isolated atria, previously loaded with [3H]-noradrenaline. The stimulation-induced release of 3H transmitter was measured in the presence of cocaine, and adrenaline was used as a facilitatory beta-adrenoceptor agonist. 2. Adrenaline (0.1 and 2 nM) increased, by about 50%, the evoked efflux of tritium. With phenoxybenzamine present, the same activity was shown with 10 nM adrenaline. 3. The beta 2-selective adrenoceptor blocking drugs: IPS 339 and ICI 118 551 caused a concentration-dependent decrease in the activity of adrenaline. Cardioselective beta-blocking drugs: acebutolol, beta-xolol, nebivolol and its isomers (R 67 138 and R 67 145) also reduced dose-dependently the agonistic action of adrenaline. The order of potency for nebivolol and its isomers was R 67 138 greater than nebivolol greater than R 67 145. The activity of pindolol was not concentration-dependent. The inhibitory effect of acebutolol was also observed in the presence of blockade of alpha-adrenoceptors. 4. The postsynaptic beta-adrenoceptor blocking activity of nebivolol and its isomers was studied in pithed rats. They reduced isoprenaline-induced tachycardia without altering hypotensive responses. The order of potency was: R 67 138 greater than nebivolol greater than R 67 145. 5. It is concluded that in rat isolated atria, presynaptic beta 2- and beta 1-adrenoceptors coexist and that facilitatory beta 1-adrenoceptors are stereospecific.
Topics: Acebutolol; Adrenergic beta-Antagonists; Animals; Decerebrate State; Electric Stimulation; Epinephrine; Heart; In Vitro Techniques; Male; Myocardium; Norepinephrine; Phenoxybenzamine; Rats; Rats, Inbred Strains; Receptors, Adrenergic, beta; Stereoisomerism; Synapses
PubMed: 2572291
DOI: 10.1111/j.1476-5381.1989.tb16884.x -
British Journal of Pharmacology May 1978Binding of [3-H]-dihydroalprenolol ([3-H]-DHA) to rat cardiac membranes was rapid and reversible (k1 = 0.633-0.701 x 10(6) M(-1) S(-1) And k(-1) = 0.0017-0.0043 s(-1). 2...
Binding of [3-H]-dihydroalprenolol ([3-H]-DHA) to rat cardiac membranes was rapid and reversible (k1 = 0.633-0.701 x 10(6) M(-1) S(-1) And k(-1) = 0.0017-0.0043 s(-1). 2 [3-H]-DHA bound to a single class of binding sites with an equilibrium dissociation constant (Kd25degreesc) of 5.7+/-1.1 x 10(-9) M. 3 This binding was specific and the order of potency of adrenoceptor agonists in competing for the binding sites was (-)-isoproterenol greater than (+/-)-isoproternol greater than (+)-isoproterenol greater than (-)-adrenaline greater than (-)-noradrenaline. This was in agreement with the beta1 nature of the cardiac beta-receptors. 4 Cardioselective beta-blockers (i.e. metoprolol, acebutolol and practolol) were shown to have lower binding site affinities, when compared to other blockers. This may be related to steric hindrance by the side-chain at the aromatic end of these molecules.
Topics: Adrenergic beta-Antagonists; Alprenolol; Animals; Drug Evaluation, Preclinical; Heart; In Vitro Techniques; Male; Protein Binding; Radioligand Assay; Rats; Receptors, Adrenergic
PubMed: 25687
DOI: 10.1111/j.1476-5381.1978.tb07787.x