Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Practolol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 775 records · Page 43Linked to original sources
PubMed1983

Adrenergic regulation of glycogenolysis in isolated guinea-pig hepatocytes: evidence that beta 2-receptors mediate catecholamine stimulation of glycogenolysis.

Glycogenolysis in hepatocytes isolated from fed guinea pigs was much more enhanced by the beta-agonist, isoproterenol, than by equimolar concentrations of the alpha-agonists, phenylephrine and norepinephrine. The stimulatory effects of catecholamines occurred with the following order of potency: isoproterenol greater than epinephrine greater than norepinephrine. This order of potency is characteristic of beta 2-adrenergic receptors. That beta 2-receptors are responsible for mediating catecholamine stimulation of glycogenolysis in guinea-pig hepatocytes was further deduced from the inhibition of agonist-stimulated glycogenolysis by beta-receptor sub-type-selective antagonists. Thus, IPS 339, a beta-antagonist which has higher affinity at beta 2-sites than at beta 1-sites, was three orders of magnitude more potent in inhibiting isoproterenol-stimulated glycogenolysis than either atenolol or practolol, both of which are beta 1-selective antagonists. The beta 2-agonists zinterol and procaterol also stimulated glycogenolysis in hepatocytes and their effects were inhibited by propranolol and IPS 339, but not by practolol. Furthermore, activation of phosphorylase in these hepatocytes by isoproterenol, epinephrine, and norepinephrine also occurred with the potency order expected for beta 2-receptors. These results are in sharp contrast to those obtained with rat hepatocytes and emphasize that species differences occur in the regulation of hepatic glycogenolysis by catecholamines.

Animals↗
PubMed1985

Inhibition of purified lysosomal phospholipase A1 by beta-adrenoceptor blockers.

Inhibition of rat liver lysosomal phospholipases is one of the main events that leads to accumulation of tissue phospholipids during drug-induced phospholipidosis. Drug inhibition of lysosomal phospholipase A may occur by direct effects of drugs on the enzyme (or substrate) or by drug-induced increases in intralysosomal pH. Although beta-adrenoceptor blockers have not been reported to cause lipid storage, they do inhibit lysosomal phospholipase A. To investigate the structural requirements for drug inhibition, we studied the effects of six beta-adrenoceptor blockers on purified rat liver lysosomal phospholipase A1. The agents studied include: propranolol, timolol, metoprolol, practolol, atenolol and the combined alpha and beta adrenoceptor blocking agent, labetalol. The drugs varied by two logs in their abilities to inhibit phospholipase A1 activity. The relative inhibitory potencies were propranolol greater than labetalol much greater than timolol greater than metoprolol much greater than practolol greater than atenolol. Our studies identify drug hydrophobicity as a key determinant for phospholipase A1 inhibition. A strong negative correlation was noted between the octanol/water partition coefficients and IC50 for phospholipase inhibition (r = -0.91). The ability of propranolol to inhibit phospholipase A1 was identical for the d, l and the d and l stereoisomers.

Adrenergic beta-Antagonists↗
PubMed1981

Cyclic AMP-generating systems in rat hippocampal slices.

Properties of the norepinephrine (NE) stimulated, cAMP-generating system were studied in rat hippocampal slices. NE but not other putative neurotransmitters, caused a 3--4-fold rise in cAMP levels in the slices. All 3 main subdivisions of the hippocampus (HPC), the dentate gyrus, areas CA3 and CA1, possessed the capacity to produce cAMP. The latency to the NE stimulation of cAMP formation was about 20 sec but maximal stimulation was reached only after 5--10 min of incubation. Intrahippocampal injection of kainic acid (KA) caused a nearly complete destruction of hippocampal neurons and a marked increase in number of glial cells. NE caused a 12--15-fold rise in cAMP levels in KA-treated HPC. Compared to normal HPC where potency order of noradrenergic agonists indicated activation of a beta-1 receptor type, the pattern for the KA-treated HPC indicated the dominance of beta-2 receptors. The beta-1 antagonist, practolol, and the beta-2 antagonist, H35/25, were about equipotent in blocking the NE-stimulated cAMP formation in normal HPC. In KA-treated HPC, on the other hand, H35/25 was much more potent than practolol in inhibiting NE-stimulated cAMP formation. It is suggested that in the HPC beta-1 adrenergic receptors are primarily neuronal and beta-2 receptors, glial, and that activation of both receptor species results in activation of a cAMP-generating system.

Adenosine↗
PubMed1988

Adrenergic and VIP stimulation of cyclic AMP accumulation in ovine pineals.

In vitro autoradiography of [125I]cyanopindolol ([125I]cyp) binding to sections of ovine pineal reveals a uniform distribution of beta-adrenergic receptors throughout the gland. Norepinephrine (NE) stimulated cyclic AMP production in pineal slices in both a time- and dose-dependent manner, producing a maximal two-fold increase. NE, isoproterenol (ISO) and epinephrine (E) stimulate cyclic AMP (cAMP) production with equal potency. NE stimulation of cAMP was totally blocked by propranolol (beta antagonist) but only partially blocked by practolol (a beta 1 preferential antagonist) indicating a mixed population of beta 1 and beta 2 receptor subtypes. Displacement of [125I]cyp binding by either practolol or zinterol (preferential beta 2 agonist) revealed IC50s of 1.3 x 10(-5) M and 9.95 x 10(-8) M respectively, confirming a mixed population of beta 1 and beta 2 receptors. A range of peptides previously localised within the pineal by immunocytochemistry were tested at a concentration of 10(-5) M for their effect on cyclic AMP production in pineal homogenates. Only vasoactive intestinal peptide (VIP) was effective showing a dose-dependent stimulation. ISO and VIP stimulation of cAMP were additive indicating action via independent receptors.

Animals↗
PubMed1979

Isolated lung strips of guinea pigs: responses to beta-adrenergic agonists and antagonists.

Isolated lung strips of guinea pigs were examined as an in vitro model for assessing the direct effect of beta-adrenergic drugs at the level of peripheral airways. Changes in intrinsic tone of thin strips of lung parenchyma were measured with an isometric force transducer. Isoproterenol, a nonselective beta-adrenergic agonist, and several beta-adrenergic agonists, soterenol, salbutamol, metaproterenol and ritodrine elicited a dose-related relaxation of lung strip. Responses to isoproterenol were antagonized by propranolol and the selective beta blocking agents butoxamine (beta2) and practolol (beta1). These results were compared to data obtained with the same compounds on isolated guinea pig atria. All agonists except ritodrine were full agonists in the lung strip whereas isoproterenol and metaproterenol were the only full agonists in the atrial preparation. In the atria, practolol was a more effective blocker of isoproterenol responses than butoxamine, and the reverse was true for the lung strip.

Adrenergic beta-Agonists↗
PubMed1984

The rat lipolytic beta-adrenoceptor: studies using novel beta-adrenoceptor agonists.

EC50 and relative intrinsic activity values were obtained for isoprenaline, fenoterol, salbutamol, prenalterol and three new beta-adrenoceptor agonists, BRL 28410, BRL 35113 and BRL 35135 on rat white adipocyte lipolysis, rat atrial rate and tension, rat uterus tension and guinea-pig tracheal tension. Fenoterol and salbutamol were selective for tracheal and uterine responses, prenalterol was selective for atrial responses, but BRL 28410, BRL 35113 and BRL 35135 were selective for the adipocyte lipolytic response. pA2 values for propranolol, practolol, ICI 118,551 and sotalol were obtained on adipocytes, atria and trachea. pA2 values for propranolol and sotalol were much lower on adipocytes than on atria or trachea. The pA2 value for practolol was lower on adipocytes than on atria and the pA2 value for ICI 118,551 was lower on adipocytes than on trachea. Both agonist and antagonist studies therefore suggest that the rat adipocyte lipolytic receptor does not fit into the current beta 1/beta 2-adrenoceptor classification.

Adipose Tissue↗
PubMed1987

Effects of various antianginal drugs on sodium influx in rat brain synaptosomes and in rat heart muscle cells in culture.

This paper describes the inhibitory effects of several antianginal drugs on 22Na uptake of the fast Na+ channel in rat brain synaptosomes and in rat heart muscle cells in culture. Calcium antagonists like verapamil, flunarizine, perhexiline, two perhexiline derivatives IPS 629 and IPS 672, and beta-adrenoceptor antagonists like propranolol and practolol were tested. IPS 672 was the most active compound on synaptosomes and heart muscle cells (IC50 = 2.0 X 10(-6) and 2.4 X 10(-6) M respectively). The relative potencies of the Ca2+ antagonists tested on heart muscle cells were found to be IPS 672 greater than IPS 629 greater than perhexiline greater than flunarizine greater than verapamil. Verapamil was 55 and 10 times less active than IPS 672 on synaptosomes and heart cells respectively. Propranolol had an inhibitory activity comparable to that of flunarizine and was 100 times more active than practolol. It can be concluded that several antianginal drugs seems to interfere with the Na+ fast channel on rat brain and heart.

Angina Pectoris↗
PubMed1983

Involvement of alpha- and beta 1-adrenergic mechanisms in the immobility-reducing action of desipramine in the forced swimming test.

The influences of various monoaminergic agents on the immobility-reducing action of desipramine (DMI) in the forced swimming test were examined. 5-Methoxy-N,N-dimethyltryptamine and methysergide, a serotonin agonist and antagonist, respectively, did not affect the duration of immobility. Pimozide, a dopamine antagonist, prolonged the duration of immobility at a dose of 0.5 mg/kg. However, at the doses tested, these drugs had no effect on the action of desipramine. Phenoxybenzamine, an alpha-adrenergic antagonist, prolonged the duration of immobility only with the largest dose (20 mg/kg), but the action of desipramine was completely blocked by this drugs at all doses. Intracerebroventricular injection of a beta-adrenergic agonist, isoproterenol (ISO), and two selective beta 1-adrenergic antagonists, atenolol (ATE) and practolol, dose-dependently diminished and potentiated, respectively, the action of desipramine although these drugs had no effect on the duration of immobility when given alone. A beta 2-adrenergic antagonist derived from oximino-9-fluorene, (IPS 339) did not influence the duration of immobility or affect the action of desipramine. The effect of isoproterenol was almost completely blocked by the pretreatment with atenolol and practolol but not by IPS 339. Subcutaneously-injected isoproterenol did not affect the action of desipramine. Isoproterenol and atenolol had no effect on the concentration of desipramine in brain regions. Phenylephrine, a postsynaptic alpha-adrenergic agonist, reduced the duration of immobility as did desipramine, but this action was not affected by isoproterenol and atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Catecholamine and guanine nucleotide activation of skeletal muscle adenylate cyclase.

Activation of adenylate cyclase by guanine nucleotide and catecholamines was examined in plasma membranes prepared from rabbit skeletal muscle. The GTP analog, 5'-guanylyl imidodiphosphate caused a time and temperature-dependent activation of the enzyme which was persistent, the Ka was 0.05 microM. 5'-Guanylyl imidodiphosphate binding to the membranes was time and temperature dependent, KD 0.07 microM. Beta adrenergic amines accelerated the rate of 5'-guanylyl imidodiphosphate activation of the enzyme with an order of potency isoproterenol approximately soterenol approximately salbutamol greater than epinephrine greater than norephrine. Catecholamine activation was antagonized by propranolol and the beta2 antagonist butoxamine; the beta1 antagonist practolol was inactive. [3H]Dihydroalprenolol bound to the membranes and binding was antagonized by beta adrenergic agonists with an order of potency similar to the activation of adenylate cyclase and was antagonized by butoxamine but not by practolol. The data are consistent with the idea that adenylate cyclase in skeletal muscle plasma membranes is coupled to adrenergic receptors of the beta2 type.

Adenylyl Cyclases↗
PubMed1989

Classification of beta-adrenoceptors in ferret tracheal smooth muscle by pharmacological responses.

Beta-adrenoceptors in ferret tracheal smooth muscle were classified into beta 1 or beta 2 by determination of (i) the potency rank order for isoprenaline, noradrenaline and adrenaline, and (ii) apparent pA2-values for a specific beta 1-antagonist (practolol) and a specific beta 2-antagonist (ICI 118.551) and (iii) concentration-inhibition curves for procaterol, a beta-agonist showing a biphasic concentration-response curve in organs with a mixed beta 1 and beta 2 adrenoceptor population. We used in vitro tracheal rings and assessed the responses to beta-adrenoceptor agonists as inhibition of phasic contractions elicited by electrical field stimulation (2 Hz for 20 s) or relaxation of tonic contractions elicited by acetylcholine (0.5 microM). The potency rank order for the agonists was isoprenaline greater than noradrenaline approximately adrenaline indicating action through beta 1-receptors. Apparent pA2-values for the antagonists were for 1, 3 and 10 microM practolol 6.0 (SE 0.27), 6.1 (SE 0.21) and 6.3 (SE 0.03), respectively. Apparent pA2 for 0.1, 1 and 10 microM ICI 118.551 were 6.8 (SE 0.25), 6.7 (SE 0.12) and 6.1 (SE 0.14), respectively. These values agree well with published pA2-values for the action of these drugs on beta 1-adrenoceptors. However, the Schild plot for ICI 118.551 was alinear indicating a possible heterogeneity of the beta-adrenoceptors in ferret trachea. The concentration-response curve for procaterol showed the biphasic form typical for organs with a mixed beta 1 and beta 2 population. However, the lower part of the curve, reflecting stimulation of beta 2-adrenoceptors reached only 17.5% (SE 1.4) of the maximally achieved inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Evaluation of dynamic polar molecular surface area as predictor of drug absorption: comparison with other computational and experimental predictors.

The relationship between various molecular descriptors and transport of drugs across the intestinal epithelium was evaluated. The monolayer permeability (Pc) of human intestinal Caco-2 cells to a series of nine beta-receptor-blocking agents was investigated in vitro. The dynamic polar molecular surface area (PSAd) of the compounds was calculated from all low-energy conformations identified in molecular mechanics calculations in vacuum and in simulated chloroform and water environments. For most of the investigated drugs, the effects of the different environments on PSAd were small. The exception was H 216/44, which is a large flexible compound containing several functional groups capable of hydrogen bonding (PSAd,chloroform = 70.8 A2 and PSAd,water = 116.6 A2). The relationship between Pc and PSAd was stronger than those between Pc and the calculated octanol/water distribution coefficients (log Dcalc) or the experimentally determined immobilized liposome chromatography (ILC) retention. Pc values for two new practolol analogues and H 216/44 were predicted from the structure-permeability relationships of a subset of the nine compounds and compared with experimental values. The Pc values of the two practolol analogues were predicted well from both PSAd calculations and ILC retention studies. The Pc value of H 216/44 was reasonably well-predicted only from the PSAd of conformations preferred in vacuum and in water. The other descriptors overestimated the Pc of H 216/44 100-500-fold.

Adrenergic beta-Antagonists↗
PubMed1981

Electrical activity of the cerebral cortex during induced hypotension with sodium nitroprusside and trimetaphan in the cat.

A comparison of the blood flow and electrical power and an area of parietal cortex has been made in cats subjected to controlled hypotension induced with either practolol and trimetaphan or practolol and nitroprusside. In both groups it was necessary also to remove blood to achieve the required low values of arterial pressure (AP). It was found that cerebral cortical blood flow was significantly greater at mean AP of 40, 35 and 30 mm Hg during nitroprusside (NTP) as compared with trimetaphan (TMP) hypotension. The total power in the e.e.g. as assessed by the cerebral function monitor (CFM) was less depressed at mean AP 35 and 30 mm Hg during NTP hypotension. Even at mean AP 26 mm Hg with NTP, electrical power, although significantly reduced, was still 66 +/- 3% of control values. Correlation of cortical blood flow with CFM activity indicated that electrical power tended towards zero at flow values of 20-25 ml min-1 per 100 g. It is concluded that, in the parietal cortex of the lightly-anaesthetized cat, cortical blood flow and electrical power are better-maintained when hypotension is induced with NTP than with TMP.

Animals↗
PubMed1977

Beta-adrenoceptor antagonists and the release of creatine phosphokinase from hypoxic heart muscle.

The ability of several beta-adrenoceptor antagonists with partial agonist activity (dl-oxprenolol, dl-acebutolol and dl-practolol) to attenuate the release of CPK that occurs during hypoxia (pO2 less than 0.8 kPa [6 MMHg]) has been studied and compared with the protection provided by dl-propranolol. dl-propranolol attenuated the hypoxic-induced release of CPK. The activity resided in the l isomer. dl-oxprenolol, acebutolol, and practolol were either less effective than propranolol in preventing CPK release, or they exacerbated the release. The protective effect of dl-propranolol extended to the hypoxic hyperthyroid heart but not to hearts that were perfused under aerobic (pO2 greater than 80 kPa [600 mmHg]) Ca2+-free conditions.

Adrenergic beta-Agonists↗
PubMed1983

Cerebral cortical extracellular fluid H+ and K+ activities during hypotension in cats.

Cerebral cortical blood flow, electrical activity, and extracellular fluid (ECF) pH and K+ ion activities were measured in anesthetized cats (0.7% halothane 65% N2O in O2) subjected to hypotension (mean BP 30-32 and 26-28 mmHg), induced by either practolol and trimetaphan (TMP) or practolol and nitroprusside (NTP). Limited blood withdrawal was also necessary to achieve these blood pressure (BP) levels. Cerebral cortical blood flow during hypotension was greater with NTP than with TMP, and hyperemia occurred in the recovery phase after NTP but not TMP. Electrical activity also was maintained better with NTP. ECF K+ increased in five of six TMP experiments but in only one of six NTP experiments. Values of K+ greater than 15 mM were only seen in the TMP group. Release of K+ into the ECF space occurred at values of cerebral cortical oxygen delivery below 3 ml 100 g-1 min-1. ECF K+ partially recovered after the end of hypotension in all except the experiment with the highest value. A progressive and severe cerebral acidosis was seen in all experiments during induced hypotension, and values below pH 6.50 were present at the stage of K+ increase in the ECF space. It is concluded that the ability of cell membranes in the cat's cortex to maintain normal ionic gradients is depressed by hypotension to these levels with TMP, but not with NTP, and that this difference is related to better-maintained oxygen supply values during NTP hypotension.

Animals↗
PubMed1987

Effects of diet-induced hypokalaemia on the efficacy of antiarrhythmic drugs against ventricular arrhythmias evoked by coronary artery ligation in the anaesthetised rat.

The antiarrhythmic efficacies of intravenous quinidine (Q), disopyramide (D), prenylamine (P), bepridil (B), and practolol were compared in normokalaemic and dietary-induced hypokalaemic anaesthetised rats. Hypokalaemia markedly increased the severity of arrhythmias induced by coronary artery ligation and reduced the antiarrhythmic efficacy of all five drugs tested. After anaesthesia, hypokalaemia was associated with hypotension and bradycardia but not QTc prolongation. However, bradycardia was not seen in conscious hypokalaemic animals. Papillary muscles taken from hypokalaemic rats displayed a longer action potential duration but no increase in Vmax compared with tissue taken from normokalaemic animals. It is concluded that hypokalaemia in the rat causes electrophysiological disturbances which may contribute both to the observed exacerbation of ischaemia-induced arrhythmias and to the reduced efficacy of Q, D, P, and B. The reduced efficacy of practolol might be explained by other consequences of hypokalaemia.

Anesthesia↗
PubMed1988

The pharmacology of epanolol (ICI 141292)--a new beta 1-selective adrenoceptor partial agonist.

The clinical benefit of beta-adrenoceptor partial agonists is still debated. To clarify the situation, epanolol, ICI 141,292 [N-[-2-(3-o-cyanophenoxy-2-hydroxypropylamino)ethyl]-4- hydroxyphenylactamide], has been developed to assess the role of modest beta-adrenoceptor partial agonist activity in humans. Animal studies have shown that epanolol is a potent beta-adrenoceptor partial agonist with a greater affinity for beta 1- than beta 2-adrenoceptors. In vitro, the PA2 values obtained for espanolol at atrial and tracheal beta-adrenoceptors were 8.42 and 6.33, respectively (isoproterenol as agonist), giving a selectivity ratio of 123. The potency was studied in vivo in the dog, where it was also shown that as an antagonist at the cardiac beta 1-adrenoceptor, it was 18 and 40 times more potent than atenolol and practolol, respectively. Espanolol has less partial agonist activity in the rat than pindolol, but more than practolol. In this species, it is also a classical partial agonist, exhibiting agonist activity at all beta-adrenoceptor blocking doses. This is in contrast to pindolol, which caused predominantly beta-adrenoceptor blockade at low doses and partial agonist activity at higher doses. These differences were confirmed in haemodynamic studies in the dog. In contrast to many other partial agonists, the partition coefficient, log P, of epanolol in octanol and water is low (0.92).

Adrenergic beta-Agonists↗
PubMed1982

Effect of cardioselective beta-blockers on the heart rate and arterial pressure responses to laryngoscopy.

The effects of the cardioselective beta-blockers practolol (Eraldin, ICI) and metoprolol (Seloken, Hässle) were studied during microlaryngoscopy. I. v. practolol (0.4 mg/kg before and 0.2 mg/kg during anaesthesia) did not protect against increases in arterial pressure, although heart rate was reduced. Oral metoprolol (0.2 g for 4 days) reduced the level of arterial pressure both before and during anaesthesia. Variations in arterial pressure were not attenuated. Very low levels of arterial pressure were seen, and variations in arterial pressures were attenuated when metoprolol was combined with fentanyl.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

An application of receptor models to the analysis of data on beta-adrenoceptor blockade.

1. The classical single receptor competitive occupancy model accurately describes the joint action of an agonist (isoprenaline) and a beta-adrenoceptor antagonist (propranolol) or some partial agonists (dichlorisoprenaline, practolol) on the positive chronotropic response in rats which have been depleted of catacholamines. 2. The mathematical form of the model suggests that the dissociation constants of classical competitive partial agonists may be assessed using dose ratios by exactly the same method as that currently used for agonist-antagonist interactions, provided that the log dose-response curves are first suitably normalized. 3. Close agreement between the theoretical mathematical models and the experimental data can be demonstrated by statistical fitting for certain beta-adrenoceptor antagonists (propranolol, dichlorisoprenaline, practolol). 4. The model fails to describe the behaviour of other beta-adrenoceptor antagonists (oxprenolol, pindolol). A possible extension of the model to include these drugs is proposed.

Adrenergic beta-Agonists↗