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 865 records · Page 48Linked to original sources

The role of clinical drug trial methodology with respect to studies of new drugs. Clinical trials of timolol.

The use of the Randomized Clinical Trial (RCT) to assess the safety and efficacy of a new drug or treatment can provide a clear evaluation of the relative benefits and risks of the new therapy as compared to the longer-established treatment methodology. In some cases, such as insulin, the benefits are immediately apparent; in other cases, such as photocoagulation for proliferative diabetic retinopathy, the consensus is not so easily obtained, and the clinical trial can supply the answer. Furthermore, the RCT provides the opportunity to identify adverse reactions, in particular those which present with a seemingly unrelated or unexpected set of symptoms. In conducting clinical trials of timolol, researchers must be alert for beta-adrenergic antagonist effects, such as were seen with practolol, and should be especially careful to note early, mild reactions which may be the forerunners of later, more severe or irreversible adverse effects.

Diabetic Retinopathy↗

Binding of [3H]-dihydroalprenolol and [3H]-acetobutolol to human blood platelets is not related to occupancy of beta-adrenoceptors.

Binding of [3H]-dihydroalprenolol to human platelet lysates is inhibited by (+/-)-propranolol and (+/-)-butoxamine, but less effectively by (+/-) practolol. (-)-Isoprenaline causes no significant inhibition of binding where stimulation of adenylate cyclase can be shown. Binding of [3H]-acetobutolol is also inhibited by (+/-)-propranolol. "Specific" binding of [3H]-dihydroalprenolol and [3H]-acetobutolol defined by (+/-) propranolol shows a non-classical saturation curve. 50% maximal binding is observed in the range 15-25 mM. The extent of "specific" binding is 2-fold greater for [3H]-dihydroalprenolol. Similar and rapid rates of binding of [3H]-dihydroalprenolol are observed at 4 degrees C and 20 degrees C. No stereoselectivity is observed for inhibition of [3H]-dihydroalprenolol binding by (+) and (-)-propranolol. Binding of [3H]-dihydroalprenolol and [3H]-acetobutolol may relate to the lipophilic character of these radioligands and does not represent interaction with beta-adrenoceptors.

Acebutolol↗

Prostaglandin E2 synthesis elicited by adrenergic stimuli in guinea pig trachea is mediated primarily via activation of beta 2 adrenergic receptors.

Prostaglandin (PG) E2 synthesis elicited by adrenergic agonists in the guinea pig trachea has been shown to be mediated via activation of beta-adrenergic receptors. The purpose of this study was to examine arachidonic acid (AA) metabolism and to characterize the subtype of beta receptor involved in PG synthesis. [14C]AA was incubated with guinea pig tracheal rings, and the radiolabelled products were extracted from the medium. Thin layer chromatographic analysis and radioimmunoassay of the extract showed that [14C]AA was incorporated into guinea pig tracheal rings and metabolized mainly into radiolabeled and immunoreactive PGE2 (iPGE2) and smaller amounts into PGF2 alpha. Trace amounts of PGD2, TxB2 and 6-keto-PGF1 alpha but not LTB4 or LTC4 were detected by enzyme immunoassay. Incubation of guinea pig tracheal rings for 10 min with isoproterenol or salbutamol resulted in a significant increase in PGE2 synthesis (optimum concentration 0.1 microM for both compounds). In contrast, dobutamine, BRL 37344, BRL 28410, norepinephrine, phenylephrine, and xylazine (up to 1 microM) did not significantly increase PGE2 production. Isoproterenol-induced iPGE2 production was inhibited by the selective beta 2 receptor antagonist butoxamine (0.1-1.0 microM) and somewhat reduced by the beta 1 receptor antagonist practolol (1 microM). The increase in PGE2 synthesis was diminished with increasing concentrations of isoproterenol (0.5-5.0 microM) or salbutamol (0.5-1.0 microM); but it was reversed by pretreatment of tracheal rings with the protein synthesis inhibitors cycloheximide (0.9 microM) and actinomycin D (2 microM) but not by phenylisopropyl adenosine (0.1-1.0 microM), an inhibitor of adenylyl cyclase. These data suggest that isoproterenol-induced iPGE2 synthesis is primarily via activation of a beta 2 adrenergic receptor. Failure to enhance iPGE2 synthesis by a high concentration of isoproterenol is likely to be due to an induction of new inhibitory protein synthesis.

Albuterol↗

Dopamine in the hypothalamus of the cat: pharmacological characterization and push-pull perfusion analysis of sites mediating hypothermia.

Within the rostral diencephalon of the cat, 113 sites were examined for their reactivity to 2.33--14.0 microgram dopamine (DA) or 2.33--14.0 microgram norepinephrine (NE) microinjected in a volume of 0.75 microliter. During each experiment, colonic temperature was monitored and additional physiological measures were recorded continuously. In contrast to CSF controls, an intrahypothalamic injection of either catecholamine at circumscribed sites evoked a dose-dependent fall in the cat's body temperature, with NE ordinarily evoking a more profound hypothermic response. The morphological sites of maximum sensitivity were localized in the anterior hypothalamic, preoptic region. At some but not all sites, a prior microinjection of 3.5--7.0 microgram phentolamine attenuated the magnitude of the DA-induced hypothermia and delayed its onset. Conversely, at all loci, the pretreatment by the injection of this alpha-adrenergic antagonist markedly reduced the absolute magnitude of the NE-induced fall in the cat's temperature. Similar pretreatment of a reactive hypothalamic locus with a beta-adrenergic receptor blocking agent, practolol (3.5 microgram), failed to alter the hypothermia following a microinjection of DA. Either of two DA receptor antagonists, haloperidol (0.04--7.0 microgram) or d-butaclamol (0.48--1.47 microgram), when given in a sufficient dose, effectively delayed the onset of the DA-hypothermia and reduced its absolute magnitude; however, the NE-induced decline in the cat's temperature was unaffected by DA receptor blockade. Endogenous stores of DA and/or NE in the cat's hypothalamus were radio-labeled with either 3H- or 14C-catecholamines or both, microinjected through the implanted guide tube into an identified amine-sensitive site. By using push-pull cannulae, the site was subsequently perfused for 5 min with artificial CSF at a rate of 25 microliter/min with samples collected at 15 min intervals. During either the third or fourth perfusion, the ambient temperature of the cat's chamber of 22--24 degrees C was elevated to 35--45 degrees C and maintained at this level for 15 or 30 min. This environmental warming evoked a release of either DA o; NE or both amines from certain circumscribed sites within the cat's rostral hypothalamus. Overall, these results provide pharmacological, physiological and anatomical evidence for a differential role of DA in the hypothalamic mechanism which mediates the heat loss processes.

Animals↗

Stimulation of beta-adrenergic receptors and spontaneous motor activity in mice.

The effects of 3 beta-adrenergic agonists (clenbuterol, isoproterenol and salbutamol) on the spontaneous motor activity of mice were studied. The present research indicated that motor activity was significantly decreased 30 minutes after IP injection of either clenbuterol (0.06 mg/kg), isoproterenol (0.5 mg/kg) or salbutamol (2 mg/kg). Hypomotility induced by clenbuterol was also significantly antagonized by propranolol in doses ranging from 1 to 8 mg/kg and by penbutolol in doses from 0.03 to 0.5 mg/kg. However, practolol, which does not cross the blood brain barrier, did not antagonize the effect of clenbuterol. Therefore, it may be hypothesized that beta adrenergic agonists decrease motor activity by a central mechanism. It was also found that tachyphylaxis or resistance to treatment, observed in cardiovascular and bronchopulmonary systems with beta-adrenergic agonists, developed after 7 injections of clenbuterol (0.25 mg/kg IP, twice daily) in the behavioral model of spontaneous motor activity in mice.

Adrenergic beta-Agonists↗

Further evidence showing that the inhibitory action of serotonin on rat masculine sexual behavior is mediated after the stimulation of 5-HT1B receptors.

To explore whether the inhibitory actions of endogenous serotonin on rat male sexual behavior were mediated via the stimulation of the 5-hydroxytryptamine1A (5-HT1A) or 5-HT1B receptor subtypes, two series of studies were undertaken. In the first series, an attempt to block the inhibitory actions of threshold doses of the serotonin precursor 5-hydroxytryptophan (5-HTP, 50 mg/kg) by administering the beta-5-HT antagonist alprenolol (5.0 mg/kg) and the selective beta-blocker practolol (0.5 mg/kg) was made. Both antagonists effectively prevented, at least partially, the inhibitory actions of 5-HTP. In the second series, a possible synergistic effect of a subthreshold dose of 5-HTP (12.5 mg/kg) with low doses of the selective 5-HT1B agonist 1-(m-trifluoro-methylphenyl)piperazine (TFMPP,0.125 mg/kg) or the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.0625 mg/kg) was investigated. A clear synergistic inhibitory effect of 5-HTP with TFMPP was observed. All data are interpreted based upon the hypothesis suggesting a physiological inhibitory role of the 5-HT1B receptor subtype on male rat sexual behavior.

5-Hydroxytryptophan↗

Influences of selective sympathetic denervation on coronary reactive hyperemia in conscious dogs.

Mongrel dogs were chronically instrumented to measure left circumflex coronary flow, arterial pressure, left atrial pressure, ECG, heart rate and in some cases, left ventricular pressure or cardiac output. A cuff type occluder was placed distal to the flow probe. Total occlusion of the left circumflex coronary artery for one minute in unsedated, resting dogs produced reactive hyperemia with an average replacement/deficit ratio of 2.63/1. In 11 dogs, sympathetic influences were investigated by chronic surgical cardiac sympathectomy. Surgical section of all ansae subclaviae responses from 2.61/1 to 1.67/1 (P less than 0.001). Left sympathectomy alone had no effect on the replacement/deficit ratio whereas selective right sympathectomy reduced it from 2.25/1 to 1.38/1. Pharmacological blockade was used to determine beta-receptor involvement in the responses. In 9 intact dogs practolol (10 mg/kg) reduced the reactive hyperemia ratio by 12% (P less than 0.05). Propranolol (1 mg/kg) further reduced this ratio by 30% (P less than 0.001). Our results suggest that sympathetic beta influences work primarily through the right cardiac sympathetic nerves. Also, the magnitude of the response appears to be due, in part, to increased metabolic activity associated with myocardial beta 1-receptors and heart rate increase as well as active vasodilation through beta 2-receptors.

Adrenergic Fibers↗

Antagonistic effect between histamine and norepinephrine on isolated guinea-pig right atrium.

Norepinephrine (NE) and histamine (His) cause a dose related increase in the rate of the guinea pig isolated right atria. The rate increase induced by both amines has been shown to be mediated by pharmacologically different receptors. His shifted the NE CEC to the right in a non parallel fashion. Cimetidine (10(-4) mol/l) abolished this antagonism. Norepinephrine (3 X 10(-7) mol/l) shifted to the right the His CEC also in a non parallel fashion. Practolol (10(-4) mol/l) abolished this antagonism. Theophylline (10(-4) mol/l) reverted both: the antagonistic action of His related to the NE chronotropic effect and the antagonistic action of NE related to the His chronotropic effect. The reversal of the antagonism could be the result of the block of purinergic P1-receptors by theophylline. This block impairs the chronotropic effect of adenilic compounds which can function as a modulater of cardiac rate through a negative feed back mechanism.

Animals↗

Study of the contraction induced by norepinephrine and clonidine in the isolated guinea-pig ileum.

1. Norepinephrine (NE) and clonidine produce a phasic, dose-dependent contraction of the isolated guinea-pig terminal ileum. 2. The effect of NE was blocked by prazosin which produced a parallel rightward shift of the concentration-effect curve to NE, with a significant depression of maximum effects. 3. Yohimbine and indomethacin noncompetitively blocked, whereas practolol potentiated, the contractile effect of NE. 4. The contractile effect of clonidine was not antagonized by indomethacin or atropine. 5. These results suggest that the isolated guinea-pig terminal ileum has excitatory receptors sensitive to clonidine stimulation and excitatory alpha receptors sensitive to blockade by prazosin, and that the activation of the latter may be related to the activation of endogenous prostaglandin synthesis.

Animals↗

Nicotine-induced salivation in cats: effects of various drugs.

The effect of an intracerebroventricular injection of an antimuscarinic drug, ganglionic blocking agent, alpha and beta adrenergic blocking drug, antiserotonin agent or antihistamine upon salivation produced by nicotine similarly injected in the cat was investigated. Atropine and hexamethonium abolished the salivation evoked by nicotine. On the other hand, salivation induced by nicotine was not significantly altered by yohimbine, practolol, methysergide and antazoline. It is concluded that the salivation produced by nicotine is mediated via central receptors which have mixed nicotinic and muscarinic properties.

Animals↗

Ventricular tachyarrhythmias in regional myocardial hyperkalemia: efficacy of three antiarrhythmic agents.

Potassium chloride infusion into the left anterior descending coronary artery induces a sequence of events analogous to those occurring during acute transmural ischemia. These include ST elevation, intramural conduction delay, ventricular techyarrhythmias and fibrillation. The influence of antiarrhythmic agents in an intact anesthetized canine model have not previously been tested. We have evaluated the efficacy of lidocaine, procaine amide and practolol in animals during regional hyperkalemia. In the untreated, only 9% survided a 20 minute observation period. All three treatment groups exhibited a reduced incidence of tachycardia and 74% survived the test period. In each treatment group this was associated with a further prolongation of intramural conduction time in the affected wall. This antiarrhythmic efficacy, thought possibly to be due to transformation of unidirectional to bidirectional block, supports the view that modulation of transcellular potassium activity contributes to the control of ischemic arrhythmias.

Animals↗

Beta adrenergic receptors in human cavernous tissue.

Beta adrenergic receptor binding was performed with 125I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptor density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of 125iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non-linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.

Adrenergic beta-Agonists↗

Beta-adrenergic blocking agents. 22. 1-Phenoxy-3-[[(substituted-amido) alkyl]amino]-2-propanols.

The synthesis of a series of 1-phenoxy-3-[[(substituted-amido)alkyl]amino]-2-propanols is described. Many of the compounds are more potent than propanolol as beta blockers, while having cardioselectivity comparable to that of practolol, when given intravenously to anesthetized cats. The structure-activity relationships shown by this series of compounds provide further evidence that the addition of substituents to the alkylamino moeity of a beta blocker can confer cardioselectivity and that amidic substituents are remarkably effective.

Adrenergic beta-Antagonists↗

beta-Adrenergic blocking agents. 23. 1-[Substituted-amido)phenoxy]-3-[[(substituted-amido)alkyl]amino] propan-2-ols.

The synthesis of a series of 1-phenoxy-3-[(amidoalkyl)amino]propan-2-ols, in which the phenoxy ring is variously substituted with ortho and para amidic moieties, is described. Several of the compounds have beta-blocking potency comparable to that of propranolol and cardioselectivity similar to that of practolol, when given intravenously to anesthetized cats. In contrast to previous findings with cardioselective beta blockers, both ortho and para substitution give variable degrees of cardioselectivity. Potency, however, is favored by ortho substitution.

Adrenergic beta-Antagonists↗

Assessment of bronchial beta blockade after oral bevantolol.

We have applied a new method for quantitative measurement of bronchial beta adrenoceptor blockade to a new beta adrenoceptor antagonist, bevantolol. Dose-response curves to a beta agonist, albuterol, were obtained in six normal subjects by measuring specific airway conductance (sGaw) after increasing doses of inhaled albuterol. These were repeated on three separate occasions 2 hr after subjects had taken oral placebo or bevantolol (75 or 150 mg), double-blind in random order. The dose-response curves after bevantolol 75 mg were displaced in the right of placebo in four subjects and after 150 mg were displaced to the right of placebo in all subjects. The mean dose ratios for bevantolol 75 or 150 mg were 1.02 and 2.77, much the same as those obtained in the same subjects after practolol 100 and 200 mg and considerably less than that after propranolol 40 mg. The mean reductions in exercise heart rate were 25% and 29% after bevantolol 75 and 150 mg. Our data show that bronchial beta blockade after a beta blocking drug can be assessed quantitatively in many by a double-blind technique.

Adrenergic beta-Antagonists↗

The brain as a possible site for the cardiovascular effects of beta-adrenoceptor blocking agents in cats.

1. DL-Propranolol, L-propranolol, DL-alprenolol, pindolol (LB46), practolol, ICI 66082, sotalol and oxprenolol all produced prolonged falls in blood pressure and heart rate after intracerebroventricular administration in conscious normotensive cats. 2. Transient initial pressor responses and tachycardias were observed after intracerebroventricular infusions of all the beta-adrenoceptor antagonists used, except ICI 66082. 3. D-Propranolol, D-alphrenolol, procaine and lignocaine all produced initial increases in blood pressure and heart rate but did not subsequently cause any reduction in either blood pressure or heart rate. 4. The time of maximum hypotension and bradycardia after intracerebroventricular infusion of beta-adrenoceptor antagonists coincided with the maximum inhibition of the centrally mediated tachycardia observed after intracerebroventricular isoprenaline.

Adrenergic beta-Antagonists↗

Regulation of cardiac output during 2,4-dinitrophenol-induced tissue hypermetabolism in the dog.

1. Cardiac output increased in proportion to oxygen consumption in intact chloralose-anaesthetized dogs after four successive intravenous infusions of 2,4-dinitrophenol (11 mumol/kg; 2 mg/kg). 2. Splenectomy abolished the increase in cardiac output after the first three doses of 2,4-dinitrophenol. beta-Adrenoreceptor blockade by practolol, on the other hand, did not prevent the cardiac output rise after the first 2,4-dinitrophenol infusion, but further increases by 2,4-dinitrophenol infusion were abolished. When splenectomy and beta-adrenoreceptor blockade were combined, cardiac output did not increase significantly after all four doses of 2,4-dinitrophenol. 3. Cardiac output and mean systemic arterial blood pressure increased when the splenic venous blood collected after 2,4-dinitrophenol infusion was infused intraportally. 4. In a vascularly isolated, but normally innervated, lower half-body cross-perfusion preparation, cardiac output and mean systemic arterial blood pressure increased in the upper half-body when tissue hypermetabolism was produced in the cross-perfused area by 2,4-dinitrophenol. Neith pulmonary artery wedge pressure nor heart rate changed significantly. 5. This circulatory stimulation, after regional 2,4-dinitrophenol infusion, was abolished or was prevented from occurring by splenectomy. 6. It appears that the normal cardiac output response to tissue hypermetabolism requires both an intact spleen and normally functioning beta-adrenoreceptors.

Animals↗

Role of central beta-adrenoceptors on stress-induced prolactin release in rats.

Adult Wistar male rats underwent immobilization stress (IS) during forty minutes. PRL secretion presented a remarkable increase after 5 minutes, and it was higher than pre-stress values during the entire duration of the experiment. The blockade of beta-1 adrenoceptors by icv injections of practolol did not modify IS-induced PRL release. IPS 339, a selective antagonist of beta-2 adrenoceptors, also injected icv, reduced PRL secretion during stress in a dose dependent fashion. The blockade of PRL secretion due to IPS 339 was reverted by a previous icv administration of salbutamol, a classical beta-2 agonist. The data presented here suggest that central beta-2 adrenoceptors activation is an important step in the control of stress-induced PRL secretion.

Adrenergic beta-Antagonists↗