Comparative effects of acebutolol and practolol on the lipolytic response to isoprenaline.

Abstract

IThe effects of ,-adrenoceptor blockade on the metabolic responses to isoprenaline have been studied in an in vitro system of isolated fat cells and in six normal subjects. 2 The inhibitory effects of varying concentrations of acebutolol, practolol and propranolol on free fatty acid (FFA) release produced by isoprenaline (10-7 M) were compared in isolated fat cells prepared from rat epididymal adipose tissue. Acebutolol and practolol, at equimolar concentrations, showed a similar inhibitory effect whilst propranolol was approximately 100 times more potent then either drug. At 10-SM concentration of propranolol, lipolysis was virtually abolished whilst at the same molar concentration, acebutolol and practolol halved the response.3 Six healthy volunteers received three successive 15 min intravenous isoprenaline challenges (0.03 ,g kg-' min-' ) per individual experiment. The first acted as a control whilst the following two were given either after single oral doses of placebo, acebutolol or practolol. The mean (± s.e. mean) basal FFA level was 0.77 ± 0.06 mEq/1 and subsequent resting values after the administration of placebo or ,-adrenoceptor blocker were not significantly different. 4 Acebutolol inhibited the respective mean rises in FFA, produced by both post-control isoprenaline challenges, by (mean ± s.e. mean) 70 ± 4% and 84 ± 5%. The comparable figures for practolol were 33 ± 15% and 24 ± 20%. The higher serum concentration of acebutolol produced greater inhibition but correlation of log serum concentration of the drug with percentage inhibition of FFA rise did not achieve significance. 5 Administration of isoprenaline, acebutolol or practolol did not significantly alter serum glucose, triglyceride or cholesterol levels. 6 Acebutolol and practolol effectively blocked the isoprenaline-induced tachycardia. The degree of blockade produced by practolol was greater than its inhibitory effect on FFA release. The diastolic fall in blood pressure in response to isoprenaline was abolished by acebutolol suggesting that its ,-adrenoceptor blocking action encompasses peripheral vascular sites. The comparable effect with practolol was a partial inhibition of the diastolic fall.

Acebutolol metabolite plasma concentration during chronic oral therapy.

“…Our data also demonstrate different time courses of the plasma concentration of acebutolol and the acetyl metabolite (Figures 2 and 3). Because of these differences, previous studies (Gibbons et al, 1976;Kumana et al, 1975;Kaye & Long, 1976;Kaye & Dufton, 1976;Roux et al, 1975;Collins, 1975) (Lucchesi & Whitsitt, 1969). For acebutolol, however, such extrapolation may be further complicated by inter-species differences in drug metabolism.…”

“…Our data also demonstrate different time courses of the plasma concentration of acebutolol and the acetyl metabolite (Figures 2 and 3). Because of these differences, previous studies (Gibbons et al, 1976;Kumana et al, 1975;Kaye & Long, 1976;Kaye & Dufton, 1976;Roux et al, 1975;Collins, 1975) using an assay which measures both acebutolol and the acetyl metabolite as a single species cannot be considered to have provided reliable information regarding the pharmacokinetics of acebutolol or to have permitted a meaningful correlation between plasma concentration and various pharmacologic effects. Further studies will be required to assess the contribution of the acetyl metabolite to P-adrenoceptor-blockade and clinical effect in man after chronic oral administration of acebutolol.…”

“…Treatment with the ,B-adrenoceptor-blocking drug acebutolol is effective for a variety of cardiac conditions (Lewis, Bakst, Kitchiner & Gotsman, 1973;Ricks, Harrison, Bell & Winkle, 1976;Lewis, Mitna & Gotsman, 1974;Biron, Proulx, Lapointe, Nadeau & Tremblay, 1975). Several recent studies have provided data on the plasma concentration of acebutolol (Gibbons, Lant, Ashford, Collins & Pinder, 1976; Kaye, Kumana, Leighton, Hamer & Turner, 1976; Kumana, Leighton, Kaye, Turner & Hamer, 1975;Kaye & Long, 1976;Kaye & Dufton, 1976;Roux, Flouvat & Delaveau, 1975;Collins, 1975). These studies, however, use non-specific methods of assay which measure acebutolol and potential metabolites as a single species.…”

“…Several recent studies have provided data on the plasma concentration of acebutolol (Gibbons, Lant, Ashford, Collins & Pinder, 1976; Kaye, Kumana, Leighton, Hamer & Turner, 1976;Kumana, Leighton, Kaye, Turner & Hamer, 1975; Kaye & Long, 1976;Kaye & Dufton, 1976;Roux, Flouvat & Delaveau, 1975;Collins, 1975). These studies, however, use non-specific methods of assay which measure acebutolol and potential metabolites as a single species.…”

Blockade of isoprenaline‐induced changes in plasma free fatty acids, immunoreactive insulin levels and plasma renin activity in healthy human subjects, by propranolol, pindolol, practolol, atenolol, metoprolol and acebutolol.

“…heart and adipose tissue as fil. However, a considerable number of reports indicate that there are differences between the pharmacological characteristics of cardiac and adipose tissue fiadrenoceptors, both in animals and in man (Harms, Zaagsma & van der Wal, 1974;Goldberg, Joffe, Bersohn, Van As, Krut & Seftel, 1975;Gibbons et al, 1975;Harms, 1976b). Comparison of the antagonist potencies of several cardioselective P-adrenoceptor blocking agents on human cardiac, bronchial and adipocyte fl-adrenoceptors against isoprenaline induced effects (Harms & van der Meer, 1975;Harms, 1976a) also suggests that these agents are somewhat less effective in blocking adipocyte fl-adrenoceptors than cardiac,B-adrenoceptors.…”