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PubMed1977

After practolol.

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Drug Evaluation↗
PubMed1977

Influence of intrinsic sympathomimetic activity and cardioselectivity on beta adrenoceptor blockade.

Dose-response curves for propranolol and oxprenolol were studied in healthy volunteers, with a standardized excercise test and percentage reduction in excercise heart rate (EHR) as the index of drug effect. The dose-response curves obtained were compared with similar curves previously reported for sotalol, practolol, and atenolol with identical experimental methods. Two distinct types of response were identified: in the first, shown by propranolol and sotalol, increasing doses of the beta adrenoceptor-blocking drug continued to produce increasing effects to the limits of the dose levels examined; with the second (oxprenolol and practolol), increasing the dose initially resulted in substantial increase in effect but subsequently larger doses produced almost no increase in effect. Consideration of the additional properties of these beta adrenoceptor-blocking drugs revealed that both practolol and oxprenolol have intrinsic sympathomimetric activity (ISA), whereas propranolol and sotalol do not. In addition, practolol is cardioselective. Further investigation of the possible influence of ISA or cardioselectivity on beta adrenoceptor-blocking activity was undertaken by studying the effects of combinations of drugs on EHR. Sotalol produced greater effect when given 2 hr after sotalol, oxprenolol, practolol, or atenolol. When oxprenolol was given after sotalol or oxprenolol, or practolol was given after sotalol or practolol, there was no further increase in percentage reduction in EHR. When atenolol was given, the combinations of sotalol and atenolol together with two doses either of sotalol or atenolol all induced increases and similar final percentage reductions in EHR. Thus atenolol induces effects like those of sotalol, which are quite different from those of oxprenolol or practolol. The presence or absence of ISA would appear to be the important difference between these two groups of drugs: ISA would, therefore, appear to be demonstrated in man by flattening of the dose-response curves with exercise.

Adrenergic beta-Antagonists↗
PubMed1975

Cardiac and pulmonary effects of acebutolol.

In a double-blind randomised study, single intravenous doses of propranolol (0-1 mg. per kg.), practolol (1 mg. per kg.), acebutolol (1 mg. per kg.), or placebo were each administered at weekly intervals to six healthy volunteers. Forced expiratory volume in 1 second (F.E.V.1), resting and exercise heart-rate, and resting and exercise peak flow-rate (P.F.R.) were determined before and at 2, 3, 4, and 6 hours after each treatment. Venous blood-samples were also obtained at these times. Compared with placebo, resting heart-rate was reduced after all three drugs, but the corresponding differences in exercise heart-rate were much greater, more consistent, and of greater statistical significance. At 2, 3, and 4 hours when acebutolol and propranolol produced equivalent cardiac beta-blocking activity (judged by reductions in exercise heart-rate), their mean plasma concentratios were in the ratio of about 8/1; and at 2 hours when practolol and acebutolol gave rise to almost equivalent cardiac beta blockade, their mean plasma concentratio ration was 3/1. At times, reductions in F.E.V.1 and resting P.F.R. after propranolol (but not after practolol or acebutolol) were significantly greater than the corresponding changes after placebo. The reductions in exercies P.F.R. after propranolol (6 hours) and acebutolol (4 hours) (but not after practolol) were significantly greater than the changes after placebo. Changes in F.E.V.1, resting and exercise P.F.R. after propranolol, and the corresponding changes after practolol, were significantly different, all of which confirmed that practolol was more cardioselective than propranolo. In general, the reductions in F.E.V.1 and resting P.F.R. after acebutolol were slightly smaller than after propranolol, excepting at 6 hours when the difference between them was significant. The reductions in exercise P;F.R. after acebutolol and propranolol were of the same order, there being no significant differences between the two, whereas the reductions after acebutolol were clearly greater than the corresponding changes after practolol, the differences being significant at 2, 3, and 4 hours.

Acebutolol↗