Pharmacological experiments in healthy volunteers with bopindolol, a long‐acting beta‐adrenoceptor blocking drug with partial agonist activity.

Aellig, W. H.

doi:10.1111/j.1365-2125.1985.tb02713.x

Cited by 25 publications

(22 citation statements)

References 9 publications

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“…There is increasing evidence that bopindolol possesses long-acting ß-blocking action with high affinity and partial agonist activity to the ß-ARs in both healthy volunteers and animal models [9,11,13,14], suggesting that less frequent administration may be necessary than with most other ß-blockers [6,7,11]. It is well known that one active metabolite (18-502) also has strong ß-blocking action, suggesting that this metabolite also contributes to the long-lasting effects of bopindolol [2].…”

Section: Discussionmentioning

confidence: 99%

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Bopindolol: A Slowly Dissociating Antagonist from the β-Adrenoceptors in Guinea Pig Atria

Hosohata

Hattori²,

Shen³

et al. 1998

Pharmacology

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The dissociating and/or residual inhibitory effects of bopindolol from β-adrenoceptors of atria strips pretreated with this drug which was then washed out with buffers on the responses to isoprenaline were determined and compared with those of propranolol, pindolol, atenolol, and the two active metabolites of bopindolol: 18-502 and 20-785. Low concentrations of bopindolol (10^–9 to 10^–8 mol/l) and the active metabolite 18-502 (10^–9 mol/l) produced rightward shifts of the concentration-response curves. On the other hand, high concentrations of bopindolol (10^–7 mol/l) and metabolite 18-502 (10^–8 and 10^–7 mol/l) produced a reduced maximum response by isoprenaline, suggesting that these nonparallel rightward shifts have pD₂ values of 7.57 (bopindolol) and 7.67 (18-502), respectively, at 0 min after washout with buffers. Pindolol (10^–7 mol/l) and propranolol (10^–7 and 10^–8 mol/l) also produced a rightward shift of isoprenaline response curves, and these concentration-response curves in guinea pig atria strips pretreated with pindolol (10^–7 mol/l) and propranolol (10^–6 mol/l) recovered to control levels. Neither of these drugs, however, reduced the maximum response by isoprenaline. A high concentration (10^–5 mol/l) of atenolol was required for a rightward shift of the isoprenaline concentration-response curve, and this drug also did not reduce the maximum response. Thus, we conclude that bopindolol and metabolite 18-502 slowly dissociate and act as noncompetitive β-antagonists rather than easily reversible β-adrenoceptor antagonists.

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Section: Discussionmentioning

confidence: 99%

“…This may explain its long-lasting antihypertensive effects. Although these long-acting pharmacological effects of bopindolol have also been demonstrated in animal models [6], healthy volunteers [7,8], and patients with hypertension [9], the precise mechanisms are not known.…”

Section: Introductionmentioning

confidence: 99%

Bopindolol: A Slowly Dissociating Antagonist from the β-Adrenoceptors in Guinea Pig Atria

Hosohata

Hattori²,

Shen³

et al. 1998

Pharmacology

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“…Previous studies have suggested that it is a non-selective antagonist with a long duration of action of at least 24 h, suggesting that less frequent administration may be necessary than with most other P-adrenoceptor blockers (Aellig, 1982). We report a detailed study of its haemodynamic effects during exercise and passive tilting in six healthy young men.…”

Section: Introductionmentioning

confidence: 99%

Bopindolol: a new long acting beta‐receptor antagonist; its effects on haemodynamics, and on the renin response to tilting.

Turner¹,

Fj²,

Knight³

et al. 1984

Brit J Clinical Pharma

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1Oral administration of single doses of bopindolol (1-4mg) caused significant reductions in the rises of systolic blood pressure and heart rate produced by exercise; only the reduction in the rise of heart rate was significantly dose-related. 2 Resting heart rate was reduced by bopindolol. There were small effects on resting blood pressure. 3 Bopindolol caused a significant attenuation of the rise in plasma renin activity produced by passive head-up tilting to 75-85 degrees. 4 Bopindolol produced a dose-related attenuation of the increase in pulse rate evoked by passive tilting. 5 All effects 1-4 were maintained for at least 24 h. 6 There was no measurable effect on plasma potassium concentration, peak flow rate or forced expiratory volume (FEV,).

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“…The long duration of action of bopindolol found in animal experiments was confirmed in man. Forty-eight hours after an oral dose of 4 mg, about 38% of the maximum effect was still present (Aellig, 1985).…”

Section: Introductionmentioning

confidence: 99%

Relationship between plasma concentrations and cardiac beta‐ adrenoceptor blockade‐a study with oral and intravenous bopindolol.

Aellig¹,

Nüesch²,

Engel³

et al. 1986

Brit J Clinical Pharma

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1 Bopindolol, an esterified P-adrenoceptor blocking drug, was administered to nine healthy male volunteers in oral (1 mg and 4 mg) and intravenous (1 mg) doses. Plasma concentrations determined using a radio-receptor assay (RRA) and high pressure liquid chromatography (h.p.l.c.) yielded almost identical results, indicating that hydrolysed bopindolol, the major metabolite, is responsible for the pharmacological activity of the drug. 2 After intravenous administration the half-life for the formation of the hydrolysis product was about 0.3 h. The elimination of hydrolysed bopindolol from the plasma, determined with a one-compartment model occurred with a half-life of about 4 h. There were indications for a longer ,B phase of elimination with a half-life of about 8 h, which, owing to the relative insensitivity of the method for concentrations present after more than 24 h, could not be determined exactly. The absolute bioavailability of the active compound is about 70%.3 Cardiac P-adrenoceptor,blockade was determined as the reduction in exerciseinduced tachycardia. With oral doses the maximum effect was reached after 3 h (-29 beats min-' after 1 mg, -40 beats min--after 4 mg). After intravenous administration most of the effect was present after 0.5 h but the maximum effect (-33 beats min-1) was only reached at 3 h. Bopindolol possesses a long duration of action: after 48 h 33% of the maximum effect of the oral dose of 4 mg was still present. 4 A good linear correlation between the logarithm of plasma concentration and the reduction of exercise-induced tachycardia was obtained from data measured after the maximal effect had been reached. At earlier time points (i.e. before the maximal effect was reached) plasma concentrations coincided with a smaller reduction of exerciseinduced tachycardia than was achieved with identical plasma concentrations at later time points. This observation is compatible with the hypothesis that the cardiac P-adrenoceptors lie outside the plasma compartment.

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Pharmacological experiments in healthy volunteers with bopindolol, a long‐acting beta‐adrenoceptor blocking drug with partial agonist activity.

Cited by 25 publications

References 9 publications

Bopindolol: A Slowly Dissociating Antagonist from the β-Adrenoceptors in Guinea Pig Atria

Bopindolol: A Slowly Dissociating Antagonist from the β-Adrenoceptors in Guinea Pig Atria

Bopindolol: a new long acting beta‐receptor antagonist; its effects on haemodynamics, and on the renin response to tilting.

Relationship between plasma concentrations and cardiac beta‐ adrenoceptor blockade‐a study with oral and intravenous bopindolol.

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