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The Biochemical Journal Nov 1974Two peaks in cyclic AMP production in rat livers 4 and 12h after partial hepatectomy (MacManus et al., 1972) were confirmed and a third peak established at 22h, which is...
Two peaks in cyclic AMP production in rat livers 4 and 12h after partial hepatectomy (MacManus et al., 1972) were confirmed and a third peak established at 22h, which is the peak of DNA synthesis. The increases in cyclic AMP were prevented by beta-adrenergic blocking agents, propranolol and pindolol, without affecting ornithine decarboxylase induction or DNA synthesis. The alpha-blocking agents, phenoxybenzamine and phentolamine, given at the time of partial hepatectomy, delayed the rise in ornithine decarboxylase normally found 4h after operation, but did not affect DNA synthesis. If the alpha-blocking agents were given at 9-12h or 18h, the onset of DNA synthesis was delayed. Phenoxybenzamine did not affect the induction of ornithine decarboxylase in intact rat livers by glucagon or growth hormone, but did inhibit induction by dexamethasone. The induction of ornithine decarboxylase produced by dexamethasone was inhibited by 17alpha-hydroxy-progesterone; this compound also blocked the induction of ornithine decarboxylase in livers of partially hepatectomized rats.
Topics: Adrenergic beta-Antagonists; Animals; Catecholamines; Cyclic AMP; DNA; Dexamethasone; Enzyme Induction; Glucocorticoids; Hepatectomy; Hydroxyprogesterones; Injections, Intraperitoneal; Liver Regeneration; Male; Ornithine Decarboxylase; Phenoxybenzamine; Phentolamine; Pindolol; Propranolol; Rabbits; Rats; Time Factors; Tritium
PubMed: 4156833
DOI: 10.1042/bj1440361 -
Canadian Medical Association Journal Jun 1984The efficacy of two beta-receptor antagonists, propranolol and pindolol, was compared with that of a calcium antagonist, verapamil, in the treatment of exertional angina... (Clinical Trial)
Clinical Trial
The efficacy of two beta-receptor antagonists, propranolol and pindolol, was compared with that of a calcium antagonist, verapamil, in the treatment of exertional angina pectoris in 22 men (mean age 51 years). The clinical response and left ventricular function were evaluated with treadmill exercise and with radionuclide ventriculography performed while the patient was at rest or exercising supine with a bicycle ergometer. All the treatments significantly prolonged exercise duration (p less than 0.001) and reduced the number of patients terminating treadmill exercise because of angina (p less than 0.05). The resting heart rate was decreased markedly (p less than 0.001) by propranolol but only slightly (p less than 0.05) by pindolol and verapamil. The left ventricular ejection fraction during rest was unchanged by any treatment, but that during exercise was improved (p less than 0.05) by all the treatments. Patients who failed to gain relief from angina with one of the drugs often responded to another, and adverse reactions occurring with one drug did not necessarily occur with another. In summary, pindolol and verapamil were safe and effective alternatives to propranolol in the treatment of the exertional angina pectoris of these patients.
Topics: Adrenergic beta-Antagonists; Adult; Aged; Angina Pectoris; Clinical Trials as Topic; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Physical Exertion; Pindolol; Propranolol; Random Allocation; Stroke Volume; Verapamil
PubMed: 6145515
DOI: No ID Found -
British Journal of Clinical Pharmacology 19871. Pindolol is a beta-adrenoceptor blocking drug with ISA (also called partial agonist activity). This means that in addition to blocking the effects of... (Review)
Review
1. Pindolol is a beta-adrenoceptor blocking drug with ISA (also called partial agonist activity). This means that in addition to blocking the effects of beta-adrenoceptor agonists, it produces some stimulation of beta-adrenoceptors. 2. In vitro studies with pindolol show that its maximum stimulant action is similar to that of isoprenaline in tissues possessing mainly beta 2-adrenoceptors, but is negligible in tissues possessing mainly beta 1-adrenoceptors. This suggests selective stimulation of beta 2-adrenoceptors. 3. In man the arteriodilator effects observed after intra-arterially infused pindolol at concentrations within the same range as those producing an antihypertensive effect also suggest a stimulant action on vascular beta 2-adrenoceptors. 4. The fact that pindolol prevents the reduction of resting heart rate and cardiac output observed after drugs lacking ISA at first sight suggests stimulation of cardiac beta 1-adrenoceptors. However, human atria possess not only beta 1- but also beta 2-adrenoceptors, stimulation of which would produce the same effect. 5. Although all beta-adrenoceptor antagonists lower blood pressure, recent experiments have shown that those agents with combined beta 1-adrenoceptor blocking activity and ISA at those receptors are less effective. This observation lends weight to the thesis that pindolol does not stimulate beta 1-adrenoceptors since it lowers blood pressure as effectively as drugs lacking ISA. 6. The evidence available therefore suggests that although pindolol blocks both beta 1- and beta 2-subtypes, it selectively stimulates beta 2-adrenoceptors.
Topics: Adrenergic beta-Antagonists; Animals; Humans; Pindolol; Sympathomimetics
PubMed: 2894222
DOI: 10.1111/j.1365-2125.1987.tb03264.x -
Zhongguo Yao Li Xue Bao = Acta... May 1989A double blind, randomised crossover study with 20 patients was performed to compare the antianginal effects of atenolol 100 mg once daily and pindolol 5 mg thrice... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
A double blind, randomised crossover study with 20 patients was performed to compare the antianginal effects of atenolol 100 mg once daily and pindolol 5 mg thrice daily. After a placebo run-in period, 2 treatments were given for 2 wk each. The number of anginal attacks and the nitroglycerin (NTG) consumption were determined. During bicycle exercise testing, the systolic blood pressure (BP), heart rate (HR), double product and exercise tolerance were measured. Both drugs reduced the number of anginal attacks and NTG consumption relative to the placebo, with atenolol being more effective than pindolol. During exercise, both beta-blockers produced a slight increase in BP and HR compared to the placebo. HR attained with atenolol was lower than pindolol at the same workload. The total duration of exercise and the maximal tolerated workload were greater in atenolol than pindolol experiment. The special properties of beta-blockers, such as cardioselectivity or intrinsic sympathomimetic activity (ISA), may have clinical importance in the treatment of angina pectoris.
Topics: Adult; Aged; Angina Pectoris; Atenolol; Blood Pressure; Double-Blind Method; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Pindolol; Random Allocation
PubMed: 2609991
DOI: No ID Found -
British Journal of Clinical Pharmacology Apr 1987Eight diabetics with autonomic neuropathy were given single oral doses of epanolol (200 mg), atenolol (50 mg), pindolol (5 mg) and placebo in a double-blind randomised... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Effects of beta-adrenoceptor blockade on heart rate and physiological tremor in diabetics with autonomic neuropathy. A comparative study of epanolol, atenolol and pindolol.
Eight diabetics with autonomic neuropathy were given single oral doses of epanolol (200 mg), atenolol (50 mg), pindolol (5 mg) and placebo in a double-blind randomised order at weekly intervals. Supine resting heart rate, physiological tremor and blood glucose were measured before, 2 and 4 h after dosing, and ambulatory heart rate monitored for 24 h. Supine resting heart rate was significantly lowered by atenolol both at 2 and 4 h, and increased on pindolol at 4 h. Heart rate was unaffected by epanolol compared with placebo. Heart rate during the 'waking' period (14.00-23.00 h) was lower than placebo after epanolol and atenolol but unaffected by pindolol. During the 'sleeping' period (23.00 h-08.00 h) heart rate was significantly increased by pindolol, lowered with atenolol and unaffected on epanolol. Pindolol significantly increased physiological tremor at 4 h. No differences were seen between epanolol, atenolol and placebo. Plasma glucose was significantly increased by pindolol 2 h after dosing. These results suggest that pindolol probably produces its partial agonist activity at both beta 1- and beta 2-adrenoceptors, while the partial agonist activity of epanolol is beta 1-selective. Despite abnormal cardiovascular reflex tests in these diabetics, the heart rate responses obtained in this study after beta-adrenoceptor blockade were surprisingly normal, and suggest that the concept of 'cardiac denervation' in diabetes requires modification.
Topics: Adrenergic beta-Antagonists; Adult; Atenolol; Benzeneacetamides; Blood Glucose; Circadian Rhythm; Diabetic Neuropathies; Electrocardiography; Heart Rate; Humans; Male; Middle Aged; Pindolol; Propanolamines; Tremor
PubMed: 2883987
DOI: 10.1111/j.1365-2125.1987.tb03066.x -
British Journal of Clinical Pharmacology 19821 Steady state concentrations and clearance of lignocaine were determine in eight healthy volunteers during 360 min continuous lignocaine infusion (2 mg/min). Before the... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
1 Steady state concentrations and clearance of lignocaine were determine in eight healthy volunteers during 360 min continuous lignocaine infusion (2 mg/min). Before the infusion propranolol (0.18 mg/kg i.v.), pindolol (0.023 mg/kg i.v.) or placebo were administered in a random double-blind, cross over design. 2 During the infusion of lignocaine heart rate, cardiac output and arterial blood pressure were measured every 60 min. 3 Propranolol decreased heart rate and cardiac output significantly by 10--20%, while pindolol or lignocaine did not change cardiac output or heart rate significantly. None of the drugs changed the arterial blood pressure. 4 Propranolol pretreatment decreased lignocaine significantly by 14.7% and the steady state concentration was increased by 22.5%. Pindolol produced no significant change in steady state concentration or clearance of lignocaine.
Topics: Adult; Cardiac Output; Drug Interactions; Heart Rate; Hemodynamics; Humans; Kinetics; Lidocaine; Male; Pindolol; Propranolol
PubMed: 7104144
DOI: 10.1111/j.1365-2125.1982.tb01915.x -
International Journal of Molecular... Sep 2020Several research disciplines require fast, reliable and highly automated determination of pharmaceutically active compounds and their enantiomers in complex biological...
Advantages and Pitfalls of Capillary Electrophoresis of Pharmaceutical Compounds and Their Enantiomers in Complex Samples: Comparison of Hydrodynamically Opened and Closed Systems.
Several research disciplines require fast, reliable and highly automated determination of pharmaceutically active compounds and their enantiomers in complex biological matrices. To address some of the challenges of Capillary Electrophoresis (CE), such as low concentration sensitivity and performance degradation linked to the adsorption and interference of matrix components, CE in a hydrodynamically closed system was evaluated using the model compounds Pindolol and Propranolol. Some established validation parameters such as repeatability of injection efficiency, resolution and sensitivity were used to assess its performance, and it was found to be broadly identical to that of hydrodynamically opened systems. While some reduction in separation efficiency was observed, this was mainly due to dispersion caused by injection and it had no impact on the ability to resolve enantiomers of model compounds even when spiked into complex biological matrix such as blood serum. An approximately 18- to 23-fold increase in concentration sensitivity due to the employment of wide bore capillaries was observed. This brings the sensitivity of CE to a level similar to that of liquid chromatography techniques. In addition to this benefit and unlike in hydrodynamically opened systems, suppression of electroosmotic flow, which is essential for hydrodynamically closed systems practically eliminates the matrix effects that are linked to protein adsorption.
Topics: Electrophoresis, Capillary; Hydrodynamics; Pharmaceutical Preparations; Pindolol; Propranolol; Reproducibility of Results; Sensitivity and Specificity; Serum; Software; Stereoisomerism
PubMed: 32961980
DOI: 10.3390/ijms21186852 -
British Journal of Pharmacology Jul 19881. In 44 patients undergoing coronary artery bypass grafting, the effect of chronic administration of the beta-adrenoceptor antagonists sotalol, propranolol, pindolol,...
1. In 44 patients undergoing coronary artery bypass grafting, the effect of chronic administration of the beta-adrenoceptor antagonists sotalol, propranolol, pindolol, metoprolol and atenolol on beta-adrenoceptor density in right atria (containing 70% beta 1- and 30% beta 2-adrenoceptors) and in lymphocytes (having only beta 2-adrenoceptors) was studied. 2. beta-Adrenoceptor density in right atrial membranes and in intact lymphocytes was assessed by (-)-[125I]-iodocyanopindolol (ICYP) binding; the relative amount of right atrial beta 1- and beta 2-adrenoceptors was determined by inhibition of ICYP binding by the selective beta 2-adrenoceptor antagonist ICI 118,551 and analysis of the resulting competition curves by the iterative curve fitting programme LIGAND. 3. With the exception of pindolol, all beta-adrenoceptor antagonists increased right atrial beta-adrenoceptor density compared to that observed in atria from patients not treated with beta-adrenoceptor antagonists. 4. All beta-adrenoceptor antagonists increased right atrial beta 1-adrenoceptor density; on the other hand, only sotalol and propranolol also increased right atrial beta 2-adrenoceptor density, whereas metoprolol and atenolol did not affect it and pindolol decreased it. 5. Similarly, in corresponding lymphocytes, only sotalol or propranolol increased beta 2-adrenoceptor density, while metoprolol and atenolol did not affect it and pindolol decreased it. 6. It is concluded that beta-adrenoceptor antagonists subtype-selectively regulate cardiac and lymphocyte beta-adrenoceptor subtypes. The selective increase in cardiac beta 1-adrenoceptor density evoked by metoprolol and atenolol may be one of the reasons for the beneficial effects observed in patients with end-stage congestive cardiomyopathy following intermittent treatment with low doses of selective beta 1-adrenoceptor antagonists.
Topics: Adrenergic beta-Antagonists; Adult; Aged; Binding, Competitive; Coronary Artery Bypass; Female; Heart; Humans; Lymphocytes; Male; Mathematical Computing; Middle Aged; Receptors, Adrenergic, beta; Software
PubMed: 2902891
DOI: 10.1111/j.1476-5381.1988.tb11576.x -
Analytical Chemistry Feb 2020Capillary electrophoresis-mass spectrometry is a powerful technique for high-throughput and high efficiency separations combined with structural identification....
Capillary electrophoresis-mass spectrometry is a powerful technique for high-throughput and high efficiency separations combined with structural identification. Electrospray ionization is the primary interface used to couple capillary electrophoresis to mass analyzers; however, improved designs continue to be reported. A new interfacing method based on vibrating sharp-edge spray ionization is presented in this work to overcome the challenges of decoupling applied voltages and to enhance the compatibility with separations performed at near-neutral pH. The versatility and ease of use of this ionization source is demonstrated using β-blockers, peptides, and proteins. The cationic β-blocker pindolol was injected electrokinetically, and detected at concentrations ranging from 10 nM to 5 μM, with an estimated detection limit of 2 nM. The vibrating sharp-edge spray ionization functions with flow rates from 70 to 200 nL/min and did not perturb the capillary electrophoresis separation electroosmotic flow as evidenced by the observation that most migration times differed less than 7% ( = 3) across a lab-built system interfaced to mass spectrometry and a commercial system that utilizes absorbance detection. For cationic beta-blockers the theoretical plates achieved in the capillary electrophoresis-mass spectrometry setup were 80%-95% of that observed with a commercial capillary electrophoresis-UV absorbance detection system.
Topics: Electroosmosis; Electrophoresis, Capillary; Molecular Structure; Pindolol; Spectrometry, Mass, Electrospray Ionization
PubMed: 31971372
DOI: 10.1021/acs.analchem.9b03994 -
Spectrochimica Acta. Part A, Molecular... May 2009Beta-adrenoceptor-blocking agents (beta-blockers) are on the list of the top selling drugs. Pindolol is a representative of this type of compound, either from the...
Beta-adrenoceptor-blocking agents (beta-blockers) are on the list of the top selling drugs. Pindolol is a representative of this type of compound, either from the structural point of view, or as reference for comparison of the pharmacokinetic properties of the beta-blockers. A study of the pindolol structure based on infrared spectroscopy and natural bond orbital (NBO) theory is the main aim of the present research. FTIR spectra of the solid pindolol were recorded from 4000 to 400cm(-1), at temperatures between 25 and -170 degrees C. For spectral interpretation, the theoretical vibrational spectra of the conformer present in the solid was obtained at the B3LYP/6-31G* level of theory. NBO analysis of the reference conformer, before and after optimization, was carried out at the same level of theory referred above. Characteristic absorption vibrational bands of the spectra of solid pindolol and of the isolated conformer were identified. Intra- and intermolecular interactions in pindolol were confirmed by the frequency shift of the vibrational modes and by the NBO theory. A detailed molecular picture of pindolol and of its intermolecular interactions was obtained from spectroscopy and NBO theory. The combination of both methods gives a deeper insight into the structure.
Topics: Adrenergic beta-Antagonists; Models, Chemical; Molecular Structure; Pindolol; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 19129004
DOI: 10.1016/j.saa.2008.11.026