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British Journal of Pharmacology Apr 1986The rat isolated right atrium (frequency response) and progesterone-treated rat uterus (relaxation) were used to examine the beta 1- and beta 2-adrenoceptor stimulatory...
The rat isolated right atrium (frequency response) and progesterone-treated rat uterus (relaxation) were used to examine the beta 1- and beta 2-adrenoceptor stimulatory effects of alprenolol, oxprenolol and pindolol. In addition, the beta 1-adrenoceptor stimulatory effect of practolol was studied in the right atrium. All the compounds studied caused a concentration-dependent increase in atrial frequency and relaxation of the uterus. The atrial response to pindolol was competitively inhibited by the beta 1-selective blocker pafenolol (10(-7) M), while the beta 2-selective blocker ICI 118551 (10(-8) M) was without effect. Pafenolol (10(-7) M) was also shown to inhibit the atrial frequency effect of alprenolol and oxprenolol. In the uterus, ICI 118551 (3 X 10(-9) M, 3 X 10(-8) M, 3 X 10(-7) M) blocked the pindolol effect with a pKB of 9.28. In addition, ICI 118551 (10(-8) M) competitively inhibited the relaxation of the uterus induced by alprenolol and oxprenolol. For alprenolol (right atrium and uterus), oxprenolol (right atrium), and pindolol (right atrium), the concentrations needed for half-maximal response were significantly greater than those required for occupation of half the receptors. This dissociation was most pronounced for pindolol in the right atrium. In this tissue, 80-85% of the beta 1-adrenoceptors had to be occupied by pindolol to initiate a tissue response corresponding to 50% of the maximal effect generated by the compound. The intrinsic activities of alprenolol, oxprenolol and pindolol (expressed as % of the maximal tissue response to isoprenaline) were significantly higher in the uterus than in the right atrium. The intrinsic activity of the compounds varied between individual preparations and, particularly in the uterus, correlated with the sensitivity of the tissue to beta-adrenoceptor stimulation by isoprenaline. 5 Calculation ofefficacy, relative to isoprenaline, of the partial beta-agonists revealed a beta 2-adrenoceptor selectivity for alprenolol (2.0), oxprenolol (1.4) and pindolol (3.0). 6 It is concluded that weak partial agonists such as alprenolol, oxprenolol and pindolol possess complex beta 1- and beta 2-adrenoceptor stimulatory properties in relation to beta-adrenoceptor occupancy and tissue sensitivity to beta-adrenoceptor stimulation.
Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Alprenolol; Animals; Female; Heart; Heart Atria; In Vitro Techniques; Isoproterenol; Male; Oxprenolol; Pindolol; Practolol; Propanolamines; Rats; Rats, Inbred Strains; Uterus
PubMed: 2871880
DOI: 10.1111/j.1476-5381.1986.tb14582.x -
British Heart Journal Jun 1981We investigated the possibility of a rebound increase in sympathetic response after stopping beta-blocker treatment by measuring heart rate under conditions of increased...
We investigated the possibility of a rebound increase in sympathetic response after stopping beta-blocker treatment by measuring heart rate under conditions of increased sympathetic drive, as provided by standing with vasodilatation, or the Valsalva manoeuvure. Significant rebound increases in heart rate were observed after stopping propranolol given for one or more weeks but not when given for only four days. The amplitude of the rebound heart rate relative to the control heart rate off beta-blockers was similar after propranolol, atenolol, oxprenolol, or acebutolol, and in hyperthyroid subjects.
Topics: Adrenergic beta-Antagonists; Angina Pectoris; Heart Rate; Humans; Hyperthyroidism; Male; Nitroglycerin; Substance Withdrawal Syndrome; Sympathetic Nervous System; Valsalva Maneuver
PubMed: 6114739
DOI: 10.1136/hrt.45.6.637 -
British Journal of Clinical Pharmacology Sep 19871 Study I evaluated the absorption of oxprenolol in the ileum, compared to jejunum, in healthy volunteers by an intestinal perfusion technique. Around 80 mg of drug were...
1 Study I evaluated the absorption of oxprenolol in the ileum, compared to jejunum, in healthy volunteers by an intestinal perfusion technique. Around 80 mg of drug were delivered as a saline solution directly in the small bowel. 2 Samples taken 30 cm distally to the site of perfusion showed that 63% of perfused oxprenolol was absorbed in the jejunum and 48% in the ileum; the differences were significant. 3 The plasma concentration-time profiles were similar for the two perfusions. The AUC and Cmax values of free and conjugated oxprenolol for the jejunal perfusion were significantly lower than those of ileum. They showed large but consistent intersubject variations in the two treatments. 4 Study II investigated, using the same technique, the influence of nutrients and digestive secretions on jejunal absorption and systemic availability of this drug. A saline (in treatments A and B) or a nutrient (in treatment C) solution containing oxprenolol was perfused into the jejunum below a balloon either inflated (A) or deflated (B and C). 5 The disappearance rate of oxprenolol from the jejunum was unaffected by endogenous secretions. The mean amount of drug absorbed along a 30-cm jejunal segment accounted for 52 (A) and 57% (B) of the total amount perfused. The intestinal absorption rate was markedly increased in the presence of nutrients (mean amount absorbed 96% for C). 6 The change in the rate of disappearance from the intestine had no effect on the systemic availability of oxprenolol (mean AUC values 8740, 8250 and 8020 nmol l-1 h for A, B and C, respectively) or its elimination from plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Biological Availability; Food; Humans; Ileum; Intestinal Absorption; Intestinal Secretions; Jejunum; Male; Oxprenolol; Perfusion
PubMed: 3663450
DOI: 10.1111/j.1365-2125.1987.tb03178.x -
British Journal of Clinical Pharmacology Nov 19821 The effects of oxprenolol and propranolol on peripheral blood flow were compared in patients with mild and moderate essential hypertension. 2 In an acute double-blind... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
1 The effects of oxprenolol and propranolol on peripheral blood flow were compared in patients with mild and moderate essential hypertension. 2 In an acute double-blind crossover study in which eight patients participated there was a significant reduction in resting forearm blood flow (RFBF) 2 h after 80 mg propranolol (mean +/- s.e. mean) (-0.87 +/- 0.13 microliter min-1 100 g-1) and after 80 mg oxprenolol (-0.30 +/- 0.12) but not after placebo. This reduction was significantly greater after propranolol (P = 0.022). 3 Seven patients continued into a double-blind crossover study comparing the above dose of the two drugs twice a day. On both the beta-adrenoceptor blockers there was a significant reduction in blood pressure after 2 weeks of treatment and also a significant reduction in RFBF. 4 After 6 weeks treatment with propranolol the reduction in RFBF persisted and was significantly less (P = 0.04) than after 6 weeks treatment of oxprenolol, at which time RFBF was back to control. 5 There were no consistent changes in skin temperature. 6 Neither propranolol nor oxprenolol should be used in patients with severe peripheral vascular disease. 7 If beta-adrenoceptor blockade is necessary in patients with mild peripheral vascular disease oxprenolol should be used in preference to propranolol but should be prescribed with caution.
Topics: Adult; Aged; Double-Blind Method; Extremities; Humans; Hypertension; Middle Aged; Oxprenolol; Propranolol; Regional Blood Flow; Time Factors
PubMed: 7138753
DOI: 10.1111/j.1365-2125.1982.tb04965.x -
British Journal of Clinical Pharmacology Mar 19791 The influence of food and plasma levels of oxprenolol was examined in healthy female volunteers using both conventional and slow-release formulations. 2 There were no... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
1 The influence of food and plasma levels of oxprenolol was examined in healthy female volunteers using both conventional and slow-release formulations. 2 There were no significant trends in plasma drug profiles due to food with either formulation. Elimination half-lives were longer after food with conventional tablets, presumably due to continued absorption. The opposite effect was seen with slow-release tablets. 3 Slow-release oxprenolol is, under the conditions of this study, a reliable and convenient dosage form, providing similar plasma-drug profiles in fasted and nonfasted individuals.
Topics: Adult; Biological Availability; Delayed-Action Preparations; Fasting; Female; Humans; Kinetics; Oxprenolol; Time Factors
PubMed: 427007
DOI: 10.1111/j.1365-2125.1979.tb00936.x -
British Journal of Sports Medicine Sep 1978Observations are presented on the electrocardiogram and plasma catecholamine concentrations of 11 healthy men monitored during two rock climbing ascents. A placebo was...
Observations are presented on the electrocardiogram and plasma catecholamine concentrations of 11 healthy men monitored during two rock climbing ascents. A placebo was administered prior to the first climb and an oral dose of the beta blocking agent oxprenolol ("Trasicor") prior to the second. Mean heart rates were 166 (+/- 20.4 SD) and 120 (+/- 10.2) respectively. Median plasma adrenaline concentrations were 0.05 microgram/1 and 0.33 microgram/1 before and after the climbs following the placebo. No significant difference was observed in the adrenaline concentrations before and after climbing following oxprenolol, or of noradrenaline concentrations on either occasion. These results are interpreted as suggesting that this popular sport represents more an anxiety-type of psychological stress than a physical stress and as such is likely to increase moral fibre rather than muscle fibre.
Topics: Adult; Anxiety; Catecholamines; Epinephrine; Fear; Heart Rate; Humans; Male; Middle Aged; Norepinephrine; Oxprenolol; Sports Medicine
PubMed: 719320
DOI: 10.1136/bjsm.12.3.125 -
British Journal of Clinical Pharmacology Dec 19811 Observations were made in five healthy subjects who exercised before and 2, 3, 6, 8 and 24 h after the oral administration on separate occasions of 160 mg oxprenolol,... (Clinical Trial)
Clinical Trial Comparative Study
1 Observations were made in five healthy subjects who exercised before and 2, 3, 6, 8 and 24 h after the oral administration on separate occasions of 160 mg oxprenolol, 160 mg slow release oxprenolol, 160 mg slow release oxprenolol with 0.25 mg cyclopenthiazide and placebo. Blood samples were obtained before and at 1, 2, 3, 6, 8, 12 and 24 h after drug administration and assayed for oxprenolol concentration. 2 The three formulations produced maximum reductions of 29% in the exercise tachycardia 3 to 6 h after drug administration. At 24 h the effects of the three preparations were not significantly different from placebo. 3 There were no significant differences in the plasma concentrations produced by the three formulations during the 24 h period. 4 These observations suggest that the slow release formulations of oxprenolol should be given twice daily to maintain cardiac beta-adrenoceptor blockade throughout a period of 24 h.
Topics: Adrenergic beta-Antagonists; Adult; Cyclopenthiazide; Delayed-Action Preparations; Drug Combinations; Heart Rate; Humans; Male; Oxprenolol; Physical Exertion; Time Factors
PubMed: 6122463
DOI: 10.1111/j.1365-2125.1981.tb01323.x -
British Journal of Clinical Pharmacology 1985A new osmotic drug delivery system (Oros) has been evaluated in multiple-dose studies in young healthy volunteers as a sustained-release vehicle for once-daily... (Clinical Trial)
Clinical Trial Comparative Study
A new osmotic drug delivery system (Oros) has been evaluated in multiple-dose studies in young healthy volunteers as a sustained-release vehicle for once-daily administration of oxprenolol. Two Oros systems were examined in two separate studies, one containing 170 mg oxprenolol succinate with an initial zero-order release rate of 10 mg/h, and the other containing 260 mg oxprenolol succinate with an initial release rate of 16 mg/h. These were compared respectively with conventional oxprenolol hydrochloride (Trasicor) 80 mg twice daily and polymer-matrix oxprenolol hydrochloride (Slow Trasicor) 160 mg once daily. Variations in mean plasma levels and beta-adrenoceptor blockade (measured by inhibition of exercise tachycardia) were considerably reduced on the 10/170 Oros once-daily compared with the Trasicor 80 mg twice-daily regimen. With both formulations there was no significant change in mean plasma concentrations or areas under the curve after 8 days' treatment, and similar pre-dose plasma concentrations were obtained. There was significant inhibition of exercise tachycardia throughout 24 h after the 10/170 Oros on the eighth day. The 16/260 Oros system gave smoother pharmacokinetic and pharmacodynamic profiles, and on repeated dosing a higher mean pre-dose plasma oxprenolol concentration than Slow Trasicor. Drug availability was similar for the two dose forms, suggesting an acceptable level of absorption of oxprenolol from most of the gastrointestinal tract. On the eighth day exercise heart rate was significantly reduced throughout 24 h with 16/260 oxprenolol Oros, but only between 1 and 15 h with Slow Trasicor.
Topics: Adult; Blood Pressure; Delayed-Action Preparations; Double-Blind Method; Female; Heart Rate; Humans; Kinetics; Male; Oxprenolol; Physical Exertion; Pulse
PubMed: 4005120
DOI: 10.1111/j.1365-2125.1985.tb02759.x -
British Medical Journal (Clinical... Sep 1984
Clinical Trial Randomized Controlled Trial
Topics: Adult; Anxiety; Clinical Trials as Topic; Female; Humans; Male; Oxprenolol; Placebos; Stress, Physiological
PubMed: 6432205
DOI: 10.1136/bmj.289.6445.592 -
Scientific Reports Jan 2021Beta-adrenergic blocking agents (abbreviated as beta-blockers) have been used for treating various cardiovascular diseases. However, the potential for asthma... (Meta-Analysis)
Meta-Analysis
Beta-adrenergic blocking agents (abbreviated as beta-blockers) have been used for treating various cardiovascular diseases. However, the potential for asthma exacerbation is one of the major adverse effects of beta-blockers. This study aimed to compare the level of risk for an asthma attack in patients receiving various beta-blockers. We searched for randomized controlled trials (RCTs) of either placebo-controlled or active-controlled design. The current network meta-analysis (NMA) was conducted under a frequentist model. The primary outcome was the incidence of asthmatic attack. A total of 24 RCTs were included. Overall NMA revealed that only oral timolol [risk ratio (RR) = 3.35 (95% confidence interval (CI) 1.04-10.85)] and infusion of propranolol [RR = 10.19 (95% CI 1.29-80.41)] were associated with significantly higher incidences of asthma attack than the placebo, whereas oral celiprolol [RR = 0.39 (95% CI 0.04-4.11)], oral celiprolol and propranolol [RR = 0.46 (95% CI 0.02-11.65)], oral bisoprolol [RR = 0.46 (95% CI 0.02-11.65)], oral atenolol [RR = 0.51 (95% CI 0.20-1.28)], infusion of practolol [RR = 0.80 (95% CI 0.03-25.14)], and infusion of sotalol [RR = 0.91 (95% CI 0.08-10.65)] were associated with relatively lower incidences of asthma attack than the placebo. In participants with a baseline asthma history, in addition to oral timolol and infusion of propranolol, oral labetalol, oxprenolol, propranolol, and metoprolol exhibited significantly higher incidences of asthma attack than did the placebo. In conclusion, oral timolol and infusion of propranolol were associated with a significantly higher risk of developing an asthma attack in patients, especially in those with a baseline asthma history, and should be avoided in patients who present a risk of asthma.Trial registration: PROSPERO CRD42020190540.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Atenolol; Bisoprolol; Cardiovascular Diseases; Celiprolol; Disease Progression; Female; Humans; Incidence; Infusions, Intravenous; Male; Practolol; Propranolol; Randomized Controlled Trials as Topic; Risk; Sotalol; Status Asthmaticus; Timolol
PubMed: 33432057
DOI: 10.1038/s41598-020-79837-3