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The latency time and escape ability of rats with learned helplessness behavior were studied after 1, 6 and 14 days of oral treatment with beta-adrenergic blockers propranolol (1 and 3 mg/kg) and acebutolol (10 and 30 mg/kg). A dose-dependent significant decrease in latency time and increase in number of avoidances was established after single, 6 and 14 days propranolol treatment. The selective beta 1-blocker acebutolol did not change the escape characteristics. These results suggest a greater impact of beta 1- than beta 2-adrenergic receptors for escape performance after unescapable foot shock, i.e., learned helplessness behavior.

The cardioselective beta-adrenoblocker acebutolol used as a course therapy for 12 weeks was found to be a highly beneficial antihypertensive agent. The antihypertensive effect of the agent given in doses of 400-800 mg/day was as pronounced and prolonged as that of propranolol, 80-160 mg/day, though there is a tendency for acebutolol to show its complete or partial antihypertensive effect rather at the end of monotherapy than propranolol. At the same time the bradycardiac effect was more pronounced in propranolol therapy. The antihypertensive effect of acebutolol, 400-800 mg/day, was revealed after 2 weeks of its use and persisted within the entire 12 weeks of therapy. The drug was well tolerated. In contrast to propranolol, a non-selective beta-adrenoblocker having no intrinsic sympathomimetic activity, acebutolol failed to produce adverse effects, such as by decreasing cardiac output and increasing total peripheral vascular resistance. The agent had a less negative chronotropic effect.

A relationship between individual variations of the oxidative and acetylating metabolism rates of penbutolol, propranolol, acebutolol which produce a hypotensive effect was studied in patients with arterial hypertension. A study was performed in groups of patients, which comprised 22, 22, and 20 males, respectively. They all suffered from Stage II hypertensive disease. There was a predominant number of patients with partial and complete antihypertensive benefits in those with low oxidation rates than in those with high oxidative metabolism rates when penbutolol (89 and 54%, respectively; p < 0.05) and propranolol (78 and 31%, respectively; p < 0.01) were given. A graphic analysis of changes in blood pressure, which had been observed during a course monotherapy with penbutolol and propranolol identified two groups of patients differing in having benefits. Within each group, the relationship between the decrease in diastolic blood pressure to the elimination half-life of parmidine is described by a linear regression equation and it has a high positive correlation coefficient.

Metoprolol and acebutolol, two supposedly cardio-selective beta-adrenergic recptor blocking agents, were tested in healthy volunteers against propranolol, a non-selective drug, for their effect on blood glucose levels during insulin-induced hypoglycaemia. There was not significant difference between propranolol and metoprolol, which both potentiated the initial hypoglycaemic action of the insulin and delayed the return to normoglycaemia. Acebutolol, even though potentiating the initial hypoglycaemia, did not possess a significant delaying effect. A similar trial should be undertaken in diabetics to determine with certainty the safety of such drugs in diabetes mellitus.

The beta-blocking potency of three doses of acebutolol (100, 200, and 600 mg three times a day) has been compared to that of propranolol (30, 60, and 180 mg three times a day) in a double-blind crossover study in 10 healthy volunteers (seven men, three women). On the basis of reduction in resting and exercise heart rates, propranolol was three to four times more potent than acebutolol on a milligram-for-milligram basis. Plasma levels showed large interindividual variation for both agents. Plasma levels were weakly correlated with the degree of beta blockade for both acebutolol (r = 0.333, p less than 0.001) and propranolol (r = 0.381, p less than 0.01). Dose and percent beta blockade were more strongly correlated (propranolol, r = 0.503, p less than 0.001; acebutolol, r = 0.574, p less than 0.001). In 11 patients (10 men, one woman) with coronary artery disease, acebutolol at 1 mg/kg infused over 15 minutes decreased heart rate and slowed conduction, increased the refractoriness of the atrioventricular node without a significant change in the atrial refractoriness, and at plasma levels greater than or equal to 1000 ng/ml slowed His-Purkinje conduction. The comparative potency data suggest that the magnitude of the decrease in the resting and exercise-induced changes in heart rate and double product, in relation to dose of acebutolol, provides quantitative indices for judging adequacy by beta blockade in clinical therapeutics. The use of plasma drug levels, however, does not appear to be helpful in judging the adequacy of beta blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

The purposes of this study were to evaluate the beta 1 and beta 2 adrenoceptor blocking properties of acebutolol and propranolol and measure the plasma levels of acebutolol, its acetylated metabolite and propranolol. Ten patients with reversible obstructive airways disease and hypertension received two separate dose levels of acebutolol and propranolol for five days each. Cardioselective properties were assessed by determining the beta 1 and beta 2 adrenergic-stimulating effects of terbutaline 5 mg before and at the end of each five-day treatment period. Both acebutolol and propranolol were clinically well tolerated. Following study drug there was a 100 percent inhibition of the beta 1 terbutaline effect, and an approximate 83 percent inhibition of the beta 2 terbutaline effect. There were no clinically significant differences between acebutolol and propranolol. The acetylated acebutolol metabolite accumulated levels two to three times higher than the parent compound, and its effects may have destroyed the cardioselectivity of acebutolol. Thus, acebutolol did not demonstrate clinically relevant cardioselectivity.

In six conscious dogs we compared the hemodynamic effects of propranolol, acebutolol, and acebutolol's primary metabolite at equipotent beta-blocking doses. Aortic pressure, heart rate, left ventricular end-diastolic pressure, dP/dt, and aortic flow velocity were measured 3 weeks after sterile surgery during three infusions of each drug. Only one drug was given on each day. The equipotent beta-blocking dose of each drug was obtained by comparing isoproterenol dose-response curves. All three drugs produced a fall in dP/dt. Left ventricular end-diastolic pressure increased in most dogs, but this was only significant for acebutolol. The heart rate tended to fall and the blood pressure rise, but this was variable and not significant. The concentration of the equipotent blocking dose of acebutolol was 44 times that of propranolol, and while the concentration of acebutolol's metabolite was 1.6 times that of acebutolol. In conclusion, at a concentration similar to acebutolol, acebutolol's metabolite has heart rate blocking and myocardial depressive effects similar to those of propranolol and acebutolol.

Pretreatment with acebutolol or propranolol at high concentrations had an inhibitory effect on the contractile response to 5-hydroxytryptamine (5-HT) in most vascular smooth muscles such as rabbit aorta and basilar, mesenteric, renal, femoral arteries and cat coronary artery. The inhibitory actions of both agents were generally greater than on the responses to excess Ca2+ and potassium. In rabbit renal arteries, acebutolol had no effect on the response to 5-HT but inhibited the responses to excess Ca2+ and potassium. Propranolol had a marked inhibitory effect on the response to 5-HT. In all preparations used, the contractions induced by norepinephrine (NE) and histamine showed a much greater resistance to the effect of acebutolol and propranolol than the contractions induced by 5-HT, Ca2+ and potassium. Nifedipine had no inhibitory effect on the response to 5-HT in most of the preparations. Nifedipine inhibited the response to 5-HT only in the basilar arteries. The inhibitory actions of propranolol on the response to 5-HT was greater than that of acebutolol. The inhibitory action of acebutolol and propranolol on the response to 5-HT may be related to mechanisms other than the beta-adrenoceptor blocking action of the drugs. The possible mechanisms of inhibitory action of both beta-adrenoceptor antagonists on 5-HT are discussed.

To assess the effects of acebutolol and propranolol on resting left ventricular function, 21 patients with coronary artery disease were studied. A baseline echocardiogram was obtained on day 1, and in a double-blind, randomized, crossover study the patients received 40 mg propranolo every 8 hr for 1 wk, 300 mg acebutolol every 8 hr for 1 wk, and 1 capsule placebo every 8 hr for 1 wk. On days 8, 15, and 22, after an echocardiogram at 7:30 A.M. (i.e., 7.5 hr after the midnight dose), they received double-blind randomized, crossover medications (acebutolol 300 mg, propranolol 40 mg, or placebo). The echocardiogram was repeated at 1.2, and 4 hr after placebo or propranolol and at 2, 3, and 5 hr after acebutolol. The left ventricular end diastolic dimension, left ventricular end systolic dimension, percent systolic shortening of the left ventricular minor axis, and ejection fraction were determined. We found that there was no significant difference between control values for any of the above parameters and those obtained at 1, 2, 4, or 7.5 hr after propranolol or placebo and at 2, 3, 5, or 7.5 hr after acebutolol. We conclude that in the doses used, acebutolol and propranolol do not induce depression of resting left ventricular function in patients with coronary artery disease who have normal or near normal left ventricular function at rest.

Systemic and coronary hemodynamic effects of acebutolol (10 mg i.v.), a cardioselective beta-adrenoceptor blocking agent were investigated in 11 patients with coronary artery disease and significant arterial obstructive lesions. Efficacy was assessed by simultaneous left and right heart catheterization and with an inlaying Webster thermodilution catheter in the coronary sinus. The data were compared with data from 7 other patients who received 2 mg i.v. of propranolol, a non-cardioselective beta-blocker. With acebutolol, (1) the heart rate was reduced significantly (p less than 0.001), (2) no significant changes were observed in the LVSP, LVEDP, mean PWP, LVmax dp/dt/p, LV negative dp/dt/p, CI, SWI and SPI, (3) CSF and MVO2 decreased significantly (p less than 0.01) 5 min after injection and (4) the CVR showed a significant elevation (p less than 0.05) after 5 min. With propranolol, (1) the heart rate decreased significantly (p less than 0.05), (2) there were no significant changes in LVSP and LVEDP, (3) the mean PWP increased significantly (p less than 0.05), (4) the LVmax dp/dt/p, CI and SWI decreased significantly (p less than 0.05), (5) the CSF and MVO2 decreased markedly (p less than 0.01) and (6) the CVR increased markedly (p less than 0.01). As compared to the effects of 2 mg i.v. of propranolol, those produced by acebutolol (10 mg i.v.) were characterized by a predominant negative chronotropic action with minimal negative inotropic action, combined with a reduction in CSF and MVO2. The findings suggest that the efficacy of acebutolol in pump failure caused by myocardial ischemia during effort angina is mediated by improvement of the myocardial oxygen demand-supply imbalance.

In 2 patients with phaeochromocytoma, effective beta-blockade was obtained with propranolol (40 mg twice a day for 3 days) or acebutolol (400 mg twice a day for 3 days) without any effect on the blood pressure. In both patients the excretion of noradrenaline predominated over that of adrenaline, a picture found in most cases of phaeochromocytoma. A hypertensive response to beta-blockade might be expected in patients with an adrenaline-secreting tumour. It cannot be a regular event or constitute a diagnostic test in patients with suspected phaeochromocytoma.

1 The effects of single evening doses of the beta-adrenoceptor blocking agents propranolol (80 mg orally) and acebutolol (200 mg orally) on plasma levels throughout the night of prolactin, growth hormone, luteinising hormone, follicle stimulating hormone, cortisol and testosterone have been studied in seven healthy male volunteers. 2 Three way analysis of variance showed that acebutolol significantly reduced circulating levels of prolactin and follicle stimulating hormone, but did not alter the levels of the other hormones studied. 3 Propranolol significantly reduced follicle stimulating hormone and testosterone, and significantly increased circulating levels of cortisol, but caused no change in the other hormones studied. 4 Prolactin, luteinising hormone, testosterone and cortisol showed a significant variation with time indicating the existence of a diurnal rhythm in the pattern of their secretion. 5 There was a significant inter-subject variability in all the hormones studied. 6 There was a significant between-subject variation in response to both propranolol and acebutolol. 7 Different subjects showed significant variations with respect to time in prolactin, growth hormone and cortisol levels. 8 Neither propranolol nor acebutolol significantly altered the time course of secretion of any of the hormones studied. 9 Possible relationships of these beta-adrenoceptor blocker-induced changes in anterior pituitary and related hormones to the antihypertensive mechanism of acebutolol and propranolol are discussed.

Intra-arterial pressure was recorded over 24 h in hypertensive patients before and during long-term treatment with beta-adrenoceptor antagonists given once daily under standardised conditions. Arterial pressure was reduced throughout the 24 h after the last dose as was variability of pressure during physical activity; variability during sleep and rest did not change significantly.

An open randomized study involving 57 subjects, 40 euthyroid and 17 hyperthyreotic, was undertaken to compare the effect of two beta-adrenergic blocking drugs, propranolol (120 mg/day) and acebutolol (600 mg/day), on the thyroid hormones serum level. In hyperthyreotic as well as in euthyroid subjects, propranolol evoked a fall in T3, an increase in reverse T3 and therefore a decrease in the T3/rT3 ratio. Acebutolol caused a decrease in T3 and in the T3/rT3 ratio only in euthyroid subjects. The only significant variation in the hyperthyroid acebutolol treated group was a decrease in reverse T3, perhaps spontaneous. TBG and TSH concentrations remained stable under treatment in all the groups. The relation of these effects with the existence of a membrane stabilizing activity displayed by propranolol as well as by acebutolol is discussed.

1 The degree of beta-adrenoceptor blockade of isoprenaline-induced tachycardia has been determined in three healthy volunteers after the administration of single oral doses of acebutolol, practolol or propranolol. 2 Plasma levels of these drugs were determined either colorimetrically (acebutolol and practolol) or fluorimetrically (propranolol). The colorimetric assay of acebutolol in plasma is fully described but the other drugs were assayed by published methods. 3 The degree of beta-adrenoceptor blockade and the plasma level for acebutolol and practolol were well correlated, whereas in the case of propranolol correlation was poor, due in part to the presence in plasma of active metabolites not detected by the fluorimetric assay. The plasma levels of practolol and propranolol are in agreement with those previously reported. 4 The maximum cardiac beta-adrenoceptor blockade achieved in this study with the respective single oral doses of acebutolol (300 mg), practolol (400 mg) or propranolol (40 mg) were similar in each of the three subjects. Therefore the beta-adrenoceptor blocking potencies of these drugs against isoprenaline-induced tachycardia are inversely related to these doses; indicating that propranolol is 7-8 times more potent than acebutolol and the latter slightly more potent than practolol.

beta-Blockers are used as if they were equivalent. With ECG recordings in 42 patients we investigated the effect on sinus heart rate of four beta-blockers given at three successive daily doses. Heart rate was dose-dependently decreased by all drugs except acebutolol, the effect of which decreased at a higher dosage. The maximal effects of metoprolol, nadolol, and propranolol were similar but the drugs differed in potency (dosage producing 50% of maximal effect, calculated from the dose-effect relationships; nadolol, 0.3 mg/day; metoprolol, 120 mg/day; propranolol, 47 mg/day). Similar relationships were found with drug plasma concentrations (concentration producing 50% of maximal effect: nadolol, 3.5 ng/ml; metoprolol, 21 ng/ml; propranolol, 36 ng/ml) and with supine or upright heart rates and blood pressures. However, the drugs were not equivalent: In addition to its greater potency, nadolol differed from propranolol and metoprolol in the slope of its dose-response curve. We conclude that beta-blockers can be compared by ECG recordings and that nadolol is different from the other beta-blockers without intrinsic sympathomimetic activity.

1 Nine hypertensive patients received by mouth daily doses of 400 mg of acebutolol and then, after a 2 week washout period, 80 mg of propranolol for 2 week periods in an open study. 2 Both treatments caused equivalent cardiac blockade as assessed by reduction in exercise tachycardia. 3 Both treatments lowered blood pressure, although this effect on pressure was better maintained in the case of acebutolol. 4 Forearm blood flow, at rest, was significantly reduced at 2 h after dosing with propranolol, but not after acebutolol. 5 This difference between the two drugs is probably due to the cardioselectivity of orally administered acebutolol in man.

Acebutolol 400 mg vs. propranolol retard 160 mg were investigated in a multicentral, double-blind, cross-over study for their action on blood pressure and heart rate in outpatients during ergometer exercise. A 2-week single-blind placebo control phase, which served as a wash-out and to eliminate placebo responders, preceded the 6-week treatment phase with propranolol (or acebutolol) followed by a further 6-week phase with acebutolol (or propranolol). At the end of each treatment phase a bicycle ergometer test was carried out, the values for 18 patients (from 26 completed investigations) were carried forward to the evaluation of the ergometry. The treatment groups were shown to be comparable. Acebutolol and propranolol produced a similar fall in systolic and diastolic blood pressure and heart rate at rest. During ergometer exercise, acebutolol led to a significantly lower increase in both systolic and diastolic blood pressure and heart rate than propranolol. The possible role of the intrinsic sympathomimetic activity (ISA) and the relative cardioselectivity of the test agents and the clinical impact of the hemodynamic findings with respect to morbidity and mortality are briefly discussed. Questioning at the end of the study revealed that significantly more patients preferred the treatment with acebutolol.

The authors studied the variations in the effects of isoprenaline hydrochloride on heart rate (beta 1) and on peripheral blood flow of the upper extremity (beta 2), determined by plethysmography, in a group of 5 men with a mean age of 31 +/- 3 years. The trial was conducted on a single-blind cross-over basis, each subject being infused over 30 min with propranolol (30 microgram/kg), acebutolol (150 microgram/kg) or a placebo (isotonic glucose solution) with at least an 8-day interval between each administration. At the end of the infusion they received isoprenaline (0.01 to 0.075 microgram/kg, in logarithmic progression) every 15 min, for 1 hour. The doses of isoprenaline were injected randomly using a latin square design. The peripheral flow, assessed by the curve of the initial part of the plethysmogram for the first 10 sec, increased with the dose of isoprenaline in the placebo series (Tg alpha = 219.9 log d + 583.4; p less than .01), did not increase in the propranolol series and increased with the dose in the acebutolol series (Tg alpha = 221.5 log d + 567.7; p less than .01); the variations in flow with isoprenaline after placebo and after acebutolol, did not differ significantly. The hear rate increased with the dose of isoprenaline in the placebo series (+55%) although tachycardia was inhibited by propranolol and acebutolol. Under the experimental conditions of this trial, propranolol inhibited beta 1 and beta 2 receptors at the same time, whereas acebutolol inhibited only beta 1 receptors.

1 The effects of acebutolol, practolol and propranolol (0,5-3 mM) on calcium uptake, calcium binding and ATPase activities of the rabbit and rat heart microsomal and mitochondrial fractions were investigated. 2 Dose-response and time course experiments revealed that propranolol greatly inhibited microsomal and mitochondrial calcium uptake whereas both acebutolol and practolol showed slight depressant effects. 3 The ATPase activities of microsomal and mitochondrial fractions were decreased by acebutolol, practolol and propranolol; however, the latter agent was more effective than the other two. 4 The inhibitory effects of acebutolol, practolol and propranolol on mitochondria and microsomes were not antagonized by adrenaline. 5 Propranolol decreased calcium binding by the microsomal fraction only, whereas acebutolol and practolol had no effect on microsomal or mitochondrial calcium binding. 6 The sensitivity of the rabbit heart subcellular fractions to the beta-adrenoceptor blocking drugs was similar to that of the rat heart; however, the calcium uptake and ATPase activities of microsomes were more sensitive to propranolol than mitochondria in both species. 7 Perfusion of rat hearts with 0.2-1 mM propranolol decreased contractile force, and microsomal and mitochondrial fractions obtained from these hearts accummulated less calcium in comparison to the control. On the other hand, acebutolol and practolol (0.2-1nM) had no appreciable effects on contractile force or subcellular fractions under similar conditions. 8 The negative inotropic effect of propranolol may partly be due to its inhibitory actions on calcium transport by subcellular organelles of the myocardium; the depressant action of propranolol on calcium transport is unlikely to be due to its beta-adrenoceptor blocking property.

In a double-blind placebo cross-over study, the beta-blocking potencies of acebutolol and propranolol were compared in ten healthy subjects under steady-state conditions of oral drug administration. Beta-adrenergic blockade, determined by the degree of attenuation of tachycardia induced by standardized multistage treadmill exercise, was correlated with dose as well as with the plasma levels of the two beta antagonists. On a weight-for-weight basis, propranolol was about 4 times as potent as acebutolol in inhibiting exercise-induced tachycardia and in reducing the heart rate times systolic blood pressure product due to exercise. A weak correlation was demonstrated between the degree of beta blockade and plasma concentrations of propranolol (r = 0.381, p less than 0.01) or acebutolol (r = 0.333, p less than 0.001), there being up to 20-24 fold interindividual variation in plasma level for a given dose of each compound. Plasma acebutolol levels were associated with at least twofold greater levels of its acetyl homologue metabolite. A positive linear correlation was found between percentage beta blockade and the corresponding doses of propranolol (r = 0.503, p less than 0.001) and of acebutolol (r = 0.574, p less than 0.001). Our overall data provide little support for the use of plasma levels of acebutolol and propranolol as a guide to beta-blocking therapy with these compounds.

1 The effect of acebutolol, a relatively selective beta-adrenoceptor blocking drug and propranolol, a non-selective one, on the hypoglycaemic action of glibenclamide after an oral glucose load has been investigated in a group of maturity-onset diabetic patients. 2 Glibenclamide significantly reduced the blood glucose levels and both acebutolol and propranolol, at therapeutic doses, were found to modify this action significantly. 3 The effect of acebutolol was slightly less than that of propranolol. The difference was not statistically significant. 4 The modes of action of sulphonylureas are reviewed and it is suggested that beta-adrenoceptor blockers may modify their effect on insulin release. This appears to be a drug interaction rather than an effect of beta-adrenoceptor blockade on glucose tolerance.

The bronchoconstrictor and beta-adrenoceptor blocking activity of (+/-)-propranolol, acebutolol and two of its analogues were compared in a group of littermate rats. Whilst the analogues of acebutolol had similar bronchoconstrictor potency to propranolol, acebutolol had considerably less activity. No correlation could be found between the degree of bronchoconstriction produced by the four drugs and their beta-adrenoceptor blocking activity in the airway smooth muscle. Acebutolol and its analogues show a wide properties could be related to the production of bronchospasm.

The acute hemodynamic effects of intravenous acebutolol, 50 mg, and propranolol, 10 mg, were evaluated in 12 patients undergoing diagnostic cardiac catheterization. Each patient received acebutolol or propranolol according to a list of randomization. Both acebutolol and propranolol depressed left ventricular function. There was a significant increase in left ventricular end-diastolic pressure at rest and after isometric exercise, with a concomitant decrease in cardiac index. Systemic vascular resistance was increased by both drugs. The increment after patients received acebutolol was not statistically significant; however, with propranolol it was statistically significant. The overall hemodynamic effects of acebutolol and propranolol are similar, but a quantitative difference exists in their effect on systemic vascular resistance. Acebutolol, a cardioselective agent, produces less of a peripheral vascular beta 2-blockade than does propranolol.

1 The cardiovascular effects of the beta-adrenoceptor blocking drugs, propranolol and acebutolol, on regional coronary blood flow and left ventricular function have been investigated in the conscious dog with developing myocardial infarction. 2 Propranolol (1 to 1.5 mg/kg) or acebutolol (4 to 5 mg/kg) were administered intravenously 2 to 3 h after occlusion of the left anterior descending coronary artery. 3 Propranolol or acebutolol administration resulted in a relative increase in flow to the ischaemic area of the myocardium, particularly to the subendocardium. 4 Propranolol produced a greater reduction in heart rate and myocardial contractility than acebutolol. 5 These results demonstrate that beta-adrenoceptor blocking drugs reduce myocardial oxygen consumption and increase coronary flow to the ischaemic area of the myocardium after coronary artery occlusion in the conscious dog.

The acute effects of propranolol and acebutolol on blood pressure, heart rate and hormonal changes during graded treadmill exercise were studied in patients with essential hypertension. Both of propranolol (2 mg i.v.) and acebutolol (10 mg i.v.) lowered the pre-exercise hemodynamic parameters and suppressed the elevation of systolic blood pressure, heart rate and pressure-rate product during exercise, but did not show any significant effect on diastolic blood pressure. Although these drugs increased plasma norepinephrine concentration (PNE) at rest and during moderate exercise, they failed to affect PNE at submaximal exercise. Plasma renin activity at rest and during exercise were more strongly suppressed by propranolol than acebutolol. Plasma aldosterone concentration was not affected by these drugs. Propranolol and acebutolol showed similar acute effects on blood pressure, heart rate and hormonal profiles at rest and during exercise within the doses used in this study. These results indicate that beta 1 adrenoceptor selectivity and intrinsic sympathomimetic activity may not play an important role in the acute antihypertensive effect at rest and during exercise and that both beta blockers have beneficial antihypertensive effects during exercise on patients with essential hypertension.

Metoprolol and acebutolol, two supposedly cardioselective beta-adrenoceptor antagonists, were tested in 11 healthy men against propranolol, a non-selective drug, for their effect on plasma free fatty acid concentrations before and after insulin. The fasting concentrations of free fatty acid were significantly reduced after acebutolol and propranolol, and their return to normal after insulin was delayed. Metoprolol had no significant effect on free fatty acid levels either before or after insulin. Although both selective and non-selective beta-blocking drugs should be expected to delay the return of free fatty acid values to normal after insulin, in contrast to propranolol and acebutolol, metoprolol had no such effect. This suggests that metoprolol may not be as effective as the other two drugs in controlling lipid metabolism during long-term treatment with beta-adrenoceptor antagonists.

In order to evaluate the long-term effects of propranolol and acebutolol on serum lipoprotein lipids, a double-blind clinical trial was carried out. Fifteen patients with stable angina pectoris, aged 32 to 79 years (mean = 53), were randomized to propranolol (80 to 160 mg/day) or acebutolol (400 mg/day) treatment groups, and followed for approximately 1 year (mean = 371 days). Blood was collected on the day treatment was begun, after approximately 5 months (mean = 158 days), and on completion of the trial. Very low-density lipoproteins (VLDL) (alpha less than 1.006), low-density lipoproteins (LDL) (1.006 to 1.063), and high-density lipoproteins (HDL) (1.063 to 1.125 [HDL2] and 1.125 to 1.21 [HDL3]) were isolated by sequential preparative ultracentrifugation, and their cholesterol and triglyceride quantified by enzymic procedures. After 1 year propranolol had raised the mean VLDL triglyceride concentration by 79% (p less than 0.005) and had lowered total HDL cholesterol by 24% (p less than 0.005). As LDL cholesterol was unchanged, the LDL cholesterol/HDL cholesterol ratio was increased by 26% (p less than 0.005). Mean values at 5 months were intermediate between those at baseline and those at 1 year. In contrast to these changes, acebutolol had no significant effect on any measured lipoprotein lipid.

Propranolol has recently been shown to produce some impairment of psychomotor performance in human volunteers. This beta-blocking compound, however, is lipophilic and readily penetrates the blood-brain barrier to gain access to the central nervous system. Acebutolol has a lower lipid solubility. A study was carried out, therefore, to compare the psychomotor effect of the two beta-blocking drugs. Any subjectively experienced side-effects were also recorded. Ten healthy volunteers were given single doses of 40 mg propranolol, 100 mg acebutolol and placebo on a random double-blind basis and the effect, if any, on performance was measured using a particularly sensitive complex reaction time technique. Propranolol produced a significant prolongation of complex reaction time when compared with placebo or acebutolol. Acebutolol did not significantly increase complex reaction time over the placebo value. Two subjects reported mild feelings of 'muzziness' after taking propranolol. No side-effects were reported after acebutolol.