benzofurans and bufuralol

Studies in 55 patients with benign essential hypertension showed that the beta-blockers bufuralol (22 patients) and propranolol (33 patients) at a dose ratio of 1:4, possess comparable antihypertensive efficacy despite different properties regarding intrinsic sympathomimetic activity. Beta-blocker-monotherapy normalized blood pressure ( less than 140/90 mm Hg) in one fourth of the patients. Body weight and plasma and blood volumes remained unchanged during beta-blockade of four to six weeks duration, the mean plasma potassium was slightly increased. The inhibition of plasma renin activity (PRA) was more pronounced with propranolol (-69%) than with bufuralol (-47%). Wirth both beta-blockers decreases in blood pressure correlated inversely with pre-treatment PRA (p less than 0.05). Propranolol-induced changes in blood pressure correlated also with associated changes in PRA (p less than 0.005); in contrast, no such relationship was observed with bufuralol. The blood pressure effects of bufuralol, however, correlated significantly with changes in urinary noradrenaline excretion (r=0.41; p less than 0.05). Patient sub-groups with low, normal or high pre-treatment PRA in the average showed a comparable pattern of pre-treatment noradrenaline excretion and patients with normal renin levels exreted more adrenaline than those with low renin levels (p less than 0.001). These data are consistent with the concept that in untreated essential hypertension PRA may be an index of adrenergic activiity, the latter representing an important determinant of blood pressure response to beta-blockade. The blood pressure lowering effects of bufuralol in benign essential hypertension seem to be independent of renin and may be related, at least partly, to diminished free peripheral noradrenaline levels.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Benzofurans; Blood Pressure; Blood Volume; Body Weight; Catecholamines; Ethanolamines; Female; Humans; Hypertension; Male; Middle Aged; Norepinephrine; Potassium; Propranolol; Renin

The hemodynamic effects of 20 mg Bufuralol-HCl and of 15 mg Propranolol given to hypertensives i.v. at rest and under physical exercise conditions were examined. It could be shown that Bufuralol-HCl lowered the diastolic BP and PR at rest already in the acute experiment, contrary to Propranolol. Under physical exercise conditions the diastolic BP is lowered, the PR remains unchanged in spite of reduced CO. After exclusion of other possible explanations, Bufuralol-HCl may lower the diastolic BP acutely at least partly by inhibition of cerebral beta-receptors. A faster and better liquor diffusion could be the reason for these results. It can be assumed that the acute BP lowering effect is mediated by the same mechanism as the chronic effect of the other beta-receptor blocking drugs.

Topics: Adrenergic beta-Antagonists; Adult; Benzofurans; Ethanolamines; Hemodynamics; Humans; Hypertension; Middle Aged; Physical Exertion; Propranolol; Rest

In this hemodynamic study a new beta-receptor blocker, Bufuralol-hydrochloride was compared with Pindolol under an Isoproterenol infusion with increasing doses in healthy male volunteers. We found the following results: 1. Before Isoproterenol peripheral resistance increased after acute i.v. application of Pindolol but decreased after Bufuralol-hydrochloride i.v. application. 2. After beta-receptor blockade with either Bufuralol-hydrochloride or with Pindolol a shift to the right of the dose effect relationship concerning heart rate and cardiac output under Isoproterenol infusion was observed, indicating beta 1-blockade. 3. The reduction of peripheral resistance which is usually observed as a sign of beta 2-blockade was also shifted to the right under the influence of both drugs. 4. This proves Bufuralol-hydrochloride to be a non-specific beta-blocking agent with an affinity to the beta 1- and beta 2-receptors. 5. Although Bufuralol-hydrochloride has a beta 2-blocking property which is even more pronounced than that of Pindolol, it reduces acutely, intravenously given, peripheral resistance.

Topics: Adrenergic beta-Antagonists; Adult; Benzofurans; Ethanolamines; Hemodynamics; Humans; Isoproterenol; Male; Pindolol; Time Factors

Topics: Adrenergic beta-Antagonists; Adult; Benzofurans; Blood Pressure; Ethanolamines; Humans; Male; Propanolamines; Pulse; Renin

Plasma concentrations of tolamolol and bufuralol (beta-blocking agents) were measured after oral and intravenous administration to healthy volunteers. The plasma levels of their main metabolite was also determined. Simultaneously, the effect of the drugs on the heart rate and blood pressure was monitored under various stimuli (isoproterenol, exercise or orthostatism) and Valsalva maneuver. When given orally, the two drugs are extensively metabolized by a hepatic first-pass effect. After reaching the systemic circulation, they are metabolized in the liver to hydroxylated derivatives with similar pharmacologic activity as the parent molecule. For tolamolol it is possible to demonstrate a good correlation between parent drug blood levels and the pharmacodynamic effect; this relation is less evident for bufuralol. The pharmacokinetic analysis of the behaviour of the two beta-blocking agents and their main metabolite makes it possible to explain this difference in part. The results of the present study emphasize the importance of measuring metabolites when dose-action relationships are investigated.

Topics: Administration, Oral; Adrenergic beta-Antagonists; Benzofurans; Blood Pressure; Dose-Response Relationship, Drug; Ethanolamines; Heart Rate; Humans; Injections, Intravenous; Liver; Propanolamines

The benzofuran analog bufuralol, a beta-adrenergic blocker, was determined in blood and urine by a specific and sensitive spectrofluorometric assay. The compound was extracted into ether from blood or urine adjusted to pH 10. The ether extract was separated by TLC to resolve the parent drug from any basic metabolites present, and the spots were eluted off the silica gel and quantitated fluorometrically in 0.1 N HCl. The overall recovery of the assay was 85 +/- 3.0%; the sensitivity limit was 2-4 ng/ml of blood or urine, using a 2.5-ml specimen/analysis. The method was applied to the determination of blood levels in a dog following a single 10-mg/kg oral dose and in two human subjects administered a single 20-mg oral dose.

Topics: Adrenergic beta-Antagonists; Animals; Benzofurans; Dogs; Ethanolamines; Humans; Methods; Spectrophotometry, Ultraviolet; Time Factors

A sensitive method for the simulataneous determination of bufuralol and its pharmacologically active metabolites in huamn plasma is described. The O-timethylsilyl,N-trifluoroacetyl derivatives are assayed by mass fragmentography. Sensitivity is 1 ng 76(-1) plasma for bufaralol and about 250 pg ml(-1) for the metabolites. An alternative procedure which uses gas chromatography with electron capture detection is also described. The sensitivity of this is about 10 ng ml(-1) plasma for all drug-related components.

Topics: Benzofurans; Chromatography, Gas; Electrons; Ethanolamines; Gas Chromatography-Mass Spectrometry; Humans; In Vitro Techniques; Ketones; Mass Spectrometry; Phenols

Topics: Adrenergic beta-Antagonists; Benzofurans; Ethanolamines

1. The mechanism of action of glucagon and epinephrine was studied in perfused rat livers. Hormone-induced transitions from one metabolic steady state to another were followed in a non-recirculating perfusion system. Glucose and lactate production rates, oxygen uptake and K+ redistribution were measured. 2. Glucagon (3 nM), cyclic AMP (0.2 mM) and epinephrine (0.5 muM) had similar effects on K+ concentrations in the perfusate. Glycogenolysis responded more rapidly and O2 uptake was enhanced to a larger extent with epinephrine than with the other agents. alpha- and beta-receptor responses were differentiated by the use of phenylephrine (0.5 muM), isoproterenol (0.5 muM) and adrenergic blocking agents (phentolamine and beta-blocker Ro 3-4787 at 0.1 mM). 3. alpha-receptors mediated an activation of glucose production that was very rapid and was paralleled by a transient decrease of K+ concentrations in the effluent from the liver, lactate production rose gradually. Respiration was also enhanced, but fell again as lactate production increased. 4. beta-receptor stimulation was followed by an increase of glucose production that was less drastic and was paralleled by a K+ release, lactate production and respiration were only slightly enhanced. beta stimulation and glucagon both resulted in an inhibition of the alpha-adrenergic effect on lactate release and simultaneously increased O2 uptake. 5. We concluded that in perfused rat livers alpha- as well as beta-adrenergic receptor stimulation resulted in an activation of glycogenolysis, possibly by two different mechanisms.

Topics: Adrenergic beta-Agonists; Animals; Benzofurans; Cyclic AMP; Epinephrine; Ethanolamines; Glucagon; Glycogen; Isoproterenol; Liver; Male; Oxygen Consumption; Perfusion; Phentolamine; Phenylephrine; Potassium; Rats; Receptors, Adrenergic