Comparison of four different beta-adrenoceptor blocking drugs on lymphocyte isoprenaline-stimulated cyclic AMP production.
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1 The influence of acebutolol, atenolol, pindolol and timolol on human lymphocyte cyclic AMP (cAMP) and its stimulation by isoprenaline in vitro has been studied. 2 Acebutolol and atenolol (10(-8)-10(-6)M) had no significant influence on lymphocyte cAMP levels or on isoprenaline-stimulated increase in cAMP. 3 Pindolol and timolol significantly antagonised the effect of isoprenaline, and pA2 values were calculated to be 8.12 and 8.04 respectively. This suggests that beta 2-adrenoceptors are involved in this phenomenon. 4 Only pindolol produced a significant increase in lymphocyte cAMP, which is consistent with its partial agonist activity. (+info)
Antihypertensive effect of diacetolol in essential hypertension.
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1 Diacetolol is the N-acetylated metabolite of acebutolol and possesses beta-adrenergic receptor blocking properties. 2 Its antihypertensive action was assessed in accordance with a double-blind randomised cross-over scheme in 17 patients with moderate essential hypertension previously well controlled with acebutolol. 3 Significant reductions in lying mean arterial blood pressure were observed with daily doses of 200 mg (- 9%), 400 mg (- 10%) and 800 mg (- 14%), and were associated with significant decreases in heart rate and plasma renin activity. 4 The diacetolol mean plasma level measured 8 to 10 h after drug ingestion was proportional to the dose (207 +/- 27, 394 +/- 63 and 823 +/- 135 ng/ml for respectively 200, 400 and 800 mg/day). (+info)
Comparison of the effects of propranolol, pindolol, oxprenolol and acebutolol on atrioventricular conduction in unanaesthetized dogs.
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1 Atrio-ventricular conduction (AVC) in the unanaesthetized dog (17 animals) was studied using atrial pacing at progressively increasing frequencies applied via electrodes implanted in the right atrium. In animals habituated to the experimental conditions, beta-adrenoceptor blocking drugs devoid of intrinsic sympathomimetic activity (ISA) modified neither heart-rate (HR) nor AVC, though 4 mg/kg i.v. propranolol transiently raised HR and facilitated AVC. Due to their ISA, pindolol and oxprenolol raised HR and facilitated AVC at high doses. 2 Thus, when not under anaesthesia, the resting dog, in contrast to man, possesses no tonic adrenergic influence which might be suppressed by beta-adrenoceptor blockings drugs. 3 After atropine or pentobarbitone, which considerably increased HR, beta-adrenoceptor blocking effects became clearly visible, and the hitherto reported depressant effects on HR and AVC were observed. However, the ISA of oxprenolol, and especially of pindolol, can partly or completely mask their beta-adrenoceptor blocking action at high doses under these experimental conditions. (+info)
Electrophysiological effects of cardioselective and non-cardioselective beta-adrenoceptor blockers with and without ISA at rest and during exercise.
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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. (+info)
Beta-adrenoceptor blocker pharmacokinetics and the oral contraceptive pill.
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Higher AUC and Cmax values were obtained for metoprolol, oxprenolol and propranolol in groups receiving the low-dose oestrogen-ethinyl oestradiol oral contraceptive, but statistical significance was reached only with metoprolol AUC. The oral contraceptive had the opposite effect on acebutolol AUC and Cmax but this was not significant. The oral contraceptive had no detectable effects on the tmax and t 1/2 values of any of the beta-adrenoceptor blockers. (+info)
Photoaffinity label for the beta-adrenergic receptor: synthesis and effects on isoproterenol-stimulated adenylate cyclase.
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An azide derivative of the beta-adrenergic antagonist acebutolol has been synthesized and its effect examined on the isoproterenol-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] activity of rat reticulocytes. It behaved as an effective competitive antagonist (Kd = 2 X 10(-7) M) prior to photolysis. However, when the reticulocyte preparation pretreated with acebutolol azide was photolyzed, a noncompetitive inhibition of isoproterenol-stimulated adenylate cyclase was obtained. Photolysis of the azide derivative in buffer alone did not convert it to a product of higher affnity. Labeling of the beta-adrenergic receptor appeared to be irreversible; multiple washings could not reverse the inhibition produced during photolysis with the label whereas washing would completely reverse the antagonism produced by the same concentration of label prior to photolysis. The effect appears to be specific for the beta-adrenergic receptor because the inhibition could be blocked stereoselectively by propranolol and there was no inhibition of fluoride- or GMP-P(NH)P-stimulated adenylate cyclase. furthermore, no effect was observed on the glucagon-mediated stimulation of adenylate cyclase of liver membranes, whereas the catecholamine response in the same membranes was inhibited. (+info)
Bronchial and cardiac beta-adrenoceptor blockade--a comparison of atenolol, acebutolol and labetalol.
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Bronchial and cardiac beta-adrenoceptor blockade have been compared in six normal subjects after three beta-adrenoceptor antagonists. Single and double doses of atenolol (50 and 100 mg), acebutolol (100 and 200 mg) and labetalolol (150 and 300 mg) were studied on separate occasions. 2 Salbutamol airway dose-response curves were obtained by measuring the airway response as the change in specific airway conductance (sGaw) after increasing doses of inhaled salbutamol. Bronchial beta-adrenoceptor blockade was assessed after each drug as the dose of salbutamol needed to cause a 50% increase in sGaw (sGaw D50). 3 Cardiac beta-adrenoceptor blockade was assessed after the same doses of each beta-adrenoceptor antagonist, by measuring the percentage reduction in exercise heart rate from control, after exercise for 5 min at 70% of the subject's maximum work rate. 4 Atenolol 50 and 100 mg caused least bronchial beta-adrenoceptor blockade and the greatest reduction in exercise heart rate. 5 Acebutolol 100 and 200 mg and labetalol 150 and 300 mg produced more bronchial beta-adrenoceptor blockade than atenolol. 6 With this approach new beta-adrenoceptor antagonists can be assessed without putting asthmatic patients at risk. (+info)
An antiidiotypic antibody that recognizes the beta-adrenergic receptor.
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Antialprenolol rabbit antibodies were fractionated on an acebutolol affinity resin, followed by L-propranolol elution so as to separate a class of binding sites that mimic the beta-adrenergic receptor. Allotype-identicaL rabbits were immunized with this fraction. After 6 mo, antisera exhibited antiidiotypic activity inhibiting [3H]alprenolol binding to the original antibody and to rabbit antiacebutolol antibodies, which had a spectrum of ligand-binding properties identical to the original idiotype. Those antisera demonstrating the original idiotype. Those antisera demonstrating the most potent antiidiotypic activity also blocked [3H]alprenolol binding to the beta-adrenergic receptor of turkey membrane, canine pulmonary membrane, and rat reticulocyte. An idiotype affinity-purified fraction showed similar activity, inhibiting beta-receptor binding with a calculated dissociation constant (KD) of 53 nM. Isoproterenol-mediated adenylate cyclase activity was also inhibited in a competitive manner. The universality of recognition of these antiidiotypic antisera indicate that the three-dimensional structure of a receptor's binding site can be modeled by a subset of an elicited antibody population. (+info)