Effects Of Bopindolol Research Articles

ボピンドロール投与による高血圧自然発症ラット(SHR)の心筋α<SUB>1</SUB>-及びβ-受容体の性状変化に関する研究

We investigated the effects of chronic administration of bopindolol in the heart of spontaneously hypertensive rats (SHR) The values of Kd and Bmax of α1 and β-adrenoceptors in the heart of SHR were calculated by Scatchard analysis used 3H-prazosin and 3H-CGP 12177 binding. In addition, their blood pressure was also determined and these effects of bopindolol were compared with those of other β-blockers. SHR were given bopindolol (1 mg/kg and 3 mg/kg), atenolol (50 mg/kg), propranolol (60 mg/kg) in drinking water during 12 weeks. The systolic blood pressure of SHR was lowered by chronic administration of bopindolol, dose-dependently observed. The chronic administration of bopindolol (3 mg/kg) to SHRs increased the Kd and Bmax values of the a lx-adrenoceptors (high affinity binding sites for 3H-prazosin). On the other hand, the administration of bopindolol (1 mg/kg and 3 mg/kg) decreased the Bmax values of the β-adrenoceptor. These findings suggest that chronic administration of bopindolol had a beneficial effect on the blood pressure and had a dose-dependent effect on the α1- and β-adrenoceptors in the heart. These effects of bopindolol maybe involved in the inhibition of the development of hypertension.

Application of the chronopharmagological methods in clinicopharmacological studies. The effect of bopindolol on the diurnal rhythm of blood pressure in patients suffering from essential hypertension

Application of the chronopharmagological methods in clinicopharmacological studies. The effect of bopindolol on the diurnal rhythm of blood pressure in patients suffering from essential hypertension

O-502 - Effects of bopindolol and its metabolites on ischemic myocardium in the anesthetized open-chest dog

O-502 - Effects of bopindolol and its metabolites on ischemic myocardium in the anesthetized open-chest dog

Bopindolol: Czechoslovak experience with a new beta blocker in the treatment of hypertension

Bopindolol is a nonselective β blocker with mild intrinsic sympathomimetic activity. One of the drug's main benefits is its prolonged effect, lasting for 24 hours, which makes it possible to administer bopindolol in a single daily dose, a fact that may improve patient adherence to therapy. A double-blind study was performed in two centers, comparing bopindolol with metoprolol in 86 hypertensive patients. Baseline diastolic blood pressure (BP) was 100 to 120 mm Hg. The effects of bopindolol or metoprolol on BP and heart rate were similar: return to normal values was achieved in 70% of patients with either drug. A 6-month study at another center found that bopindolol did not affect the levels of total cholesterol, low-density and high-density lipoprotein cholesterol or triglycerides. Another 12-month study documented a decrease in total cholesterol, apolipoprotein (apo) A1 and apo B. The apo A B ratio rose, thus improving the atherosclerotic index. No deterioration of glucose tolerance or immunoreactive insulin response to glucose was seen after 6 months of bopindolol administration. Bopindolol satisfactorily modifies not only resting but also exercise BP during isometric and isotonic load, thus reducing BP fluctuation during physical activities of the hypertensive patient. The drug exerts no effect on renal and liver function, electrolyte balance and hematologic parameters. Bopindolol is a very useful drug of first choice in mild and moderate hypertension. Bopindolol's main advantages include its prolonged action, good tolerance and a beneficial effect on risk factors of atherosclerosis (lipid and carbohydrate metabolism).

Bopindolol

Bopindolol is a nonselective beta-adrenoceptor antagonist [corrected] with partial agonist activity which is used in the treatment of hypertension. The drug is rapidly metabolised to an active hydrolysed form. The antihypertensive effects of bopindolol 0.5 to 4 mg are sustained for more than 24 hours after once daily dosing, and the drug appears similar in efficacy to propranolol, metoprolol, atenolol, pindolol and slow release nifedipine in the treatment of mild to moderate forms of this disease. In limited trials bopindolol has also successfully reduced symptoms in patients with angina pectoris, anxiety and essential tremor. Thus, bopindolol is an effective and well-tolerated beta-adrenoceptor antagonist.

Effects of bopindolol on platelet function in hypertension at rest and during exercise

The effects of bopindolol, a new nonselective β-blocking agent, on platelet function have been studied in 10 male hypertensive patients given the drug (1 mg/day) in turn for eight weeks. Bopindolol significantly (p<0.01) decreased the bicycle exercise- (1.5 W/kg body weight for 6 minutes) induced increase in platelet aggregation. During bopindolol-treatment both the slope and the height of the platelet aggregation response curve were moderately decreased at rest before exercise and significantly (p<0.05) decreased at rest after exercise. During exercise the slope amounted to 75.4±44° before and to 70.8±5.3° after therapy (p<0.01), the height to 64.0±11.9% before and to 58.1±14.7% (p<0.05) after therapy. Furthermore, bopindolol significantly increased the exercise-induced decrease in platelet sensitivity to PGI 2 (p<0.05; IC-50-value: 2.10±0.47 vs 1.88±0.31 ng/ml) and PGD 2 (p<0.05; IC-50-value: (19.88±2.10 vs 18.57±1.63 ng/ml). Bopindolol also significantly (p<0.05) decreased the exercise-induced elevation in serum-TXB 2 (244.9±35.2 vs 237.3±27.2 ng/ml) and plasma-TXB 2 (15.7±6.3 vs 13.1±3.7 pg/ml). The platelet count, the plasma levels of 6-oxo-PGF 1α, β-thromboglobulin (β-TG) and platelet factor 4 (PF4) were not affected by bopindolol. It is concluded that bopindolol favourably affects platelet function, in that it lowers exercise-induced platelet aggregation and TXB 2-formation in therapeutical doses and increases platelet sensitivity to antiaggregatory prostaglandins. Treatment of hypertension with a substance that lowers blood pressure and inhibits platelet activation might be of clinical benefit for routine application in hypertensive patients.

Haemodynamic Effects of Bopindolol and Atenolol in Coronary Artery Disease A Noninvasive Study

Bopindolol, a new non-selective betablocker, and atenolol, a conventional betablocker, were studied in parallel groups of eight normotensive patients with NYHA II-III angina pectoris. Non-invasive haemodynamic measurements were made using echocardiography and systolic time intervals. Drug doses were 1 mg bopindolol and 100 mg atenolol once daily; measurements were made immediately and at one and six weeks intervals. Both drugs reduced heart rate, atenolol from 62 to 47 beats/minute (24%, P less than 0.01) and bopindolol from 64 to 56 beats/minute (13%, P less than 0.05) at 24 hours. Only atenolol reduced mean blood pressure. Rate pressure product was persistently reduced by atenolol (30% at 24 hours), while with bopindolol this effect lessened with time. Opposite trends in left ventricular enddiastolic and endsystolic diameters were observed; with atenolol tending to increase and bopindolol to lower them. Atenolol had no influence on cardiac contractility, while bopindolol increased it, which was shown by enhancements in the fractional shortening, ejection fraction and maximum velocity of fibre shortening. Neither drug changed peripheral vascular resistance or systolic time intervals. Two patients on bopindolol left the study because of worsening symptoms of coronary artery disease, and two on atenolol owing to side effects, bradycardia and syncope in one and diarrhea in the other. In conclusion, bopindolol showed less beta-blocking effect than atenolol and it had a positive inotropic effect. Its benefit in treating coronary artery disease remains to be proved.

Effect of Bopindolol on Renin Secretion and Renal Excretory Function in Rats

We investigated the effects of the new beta-adrenoceptor antagonist, bopindolol, on stimulated renin secretion and on renal function in conscious rats. Intravenous doses of 10, 31.6, and 100 micrograms/kg of bopindolol antagonized the rise in plasma renin activity (PRA) induced by the administration of isoproterenol (10 micrograms/kg, s.c.). Peak PRA, evident at 15 min after isoproterenol, reached 27 +/- 3 ng/ml/h with bopindolol (100 micrograms/kg) pretreatment vs. 105 +/- 7 ng/ml/h in saline controls. Antagonism by bopindolol (100 micrograms/kg, i.v.) of isoproterenol-stimulated rise in PRA persisted through 12 h. Within this dosage range, bopindolol itself had no significant effect on PRA. Significant antagonism of beta-adrenoceptor-induced hypotension resulted with 31.6 and 100 micrograms/kg of i.v. bopindolol. Orally administered bopindolol produced significant antagonism of isoproterenol-induced increase in PRA at a dose of 316 micrograms/kg; however, oral doses of 31.6-316 micrograms/kg of bopindolol failed to significantly alter furosemide-stimulated increase in PRA. Bopindolol alone had little effect on renal excretory function but caused a slight attenuation of furosemide-induced diuresis and electrolyte excretion. Plasma electrolytes and osmolarity were unaffected by bopindolol alone or in conjunction with furosemide. These results indicate that bopindolol (a) is a potent, long-acting, orally active, antagonist of beta-adrenoceptor-stimulated renin secretion in the rat, (b) is ineffective in antagonizing furosemide-induced rise in PRA, (c) does not elevate basal levels of PRA by virtue of its intrinsic sympathomimetic activity, and (d) does not cause dramatic alteration of renal excretory function at effective beta-blocking doses.

Effects of bopindolol in essential hypertension

In order to assess the long-term (12 months) antihypertensive effectiveness and the tolerability of bopindolol, a non-selective β-blocker with mild partial agonist activity, an open multicentre trial was performed; this is an interim report after 6 months of treatment. Ninety-six outpatients with mild to moderate essential hypertension at the end of a 2-week placebo run-in period were enrolled in the study. The active treatment started with bopindolol (0.5–2 mg once a day); if necessary, a diuretic (chlorthalidone, in doses ranging from 25 mg every third day to 25 mg once a day) was added after 8 weeks of bopindolol monotherapy. Supine and standing systolic and diastolic blood pressures and the heart rate were recorded in basal conditions and after 2, 4, 8, 16 and 24 weeks; venous plasma and urine specimens were collected at the end of the run-in and after 8 and 24 weeks. Adverse reactions were elicited from the patients by checklist. Eighty-three patients (38 males, 45 females, mean age 47.7 years) completed the 6-month phase, while four dropped out during the run-in period and nine were withdrawn from treatment because of insufficient compliance. Under bopindolol monotherapy, blood pressure was normalized in 50 out of the 83 patients (60.2%); in 44 of these (53%) the optimal bopindolol dose was 1.0 mg once a day or less. Another 17 patients achieved blood pressure control under the combination treatment, so that the overall responder rate was 86.7% (72 out of 83 patients). Thirty-four of the 83 patients (40%) reported 50 adverse reactions (asthenia, nausea, dizziness, sleep disturbances), in most cases transient, self-limiting and mild. This rate is probably related to over-reporting due to the checklist collection procedure. No changes were observed in the laboratory parameters throughout the trial. These preliminary data indicate that bopindolol is a safe and effective drug for long-term treatment of essential hypertension.

A double-blind comparison of the anti-anxiety effects of bopindolol, lorazepam, butalbital and placebo in surgical patients

A double-blind comparison of the anti-anxiety effects of bopindolol, lorazepam, butalbital and placebo in surgical patients

Acute and long-term haemodynamic effects of bopindolol in hypertension

Acute and long-term haemodynamic effects of bopindolol in hypertension

Antihypertensive and metabolic effects of bopindolol at rest and during exercise – is once weekly dosage possible?

Antihypertensive and metabolic effects of bopindolol at rest and during exercise – is once weekly dosage possible?

Effect of Bopindolol on the Circadian Blood Pressure Profile in Essential Hypertension

The effect of bopindolol on circadian blood pressure and heart rate profile was evaluated by means of an automatic recording technique (Pressurometer II). Blood pressure and heart rate was measured every 15 min for 24 h in 11 ambulant hypertensive patients. Recordings were made after 2 weeks on placebo then after treatment for 4 and 8 weeks with single daily doses of 0.5 or 1 mg bopindolol, according to a double-blind crossover plan. The results show a significant fall in the mean 24-h values for systolic and diastolic blood pressure and heart rate on both dosages of bopindolol. The low-dose level had a more marked effect on the day phase of the blood pressure profile, whereas the high-dose level affected day and night phases equally. Over all, the circadian rhythms of blood pressure and heart rate were not influenced. In conclusion, bopindolol has a well-defined antihypertensive effect on the various phases of the 24-h blood pressure and heart rate profiles.

Effects of Bopindolol on Left Ventricular Function During Exercise in Patients with Coronary Artery Disease

Bopindolol is a new beta blocker with a long duration of action. We examined the haemodynamic effects of multiple oral doses of 2 mg in 12 male patients, with coronary artery disease. Placebo was given for 7 days followed by bopindolol 2 mg daily for 14 days. Scintigraphic ventriculography combined with an exercise test was carried out at baseline before treatment with bopindolol, and repeated after 7 and 14 days treatment. On day 7 the measurements were made 2 h after therapy (i.e., when plasma levels were maximal) and on day 14 when plasma levels were lowest (24 h after the last dose). The results showed that bopindolol had little effect on blood pressure or heart rate at rest in these normotensive patients but that both parameters measured after exercise were statistically significantly reduced (p less than 0.001). There was little difference between the effect seen 2 h after therapy and the effect seen 24 h after therapy, thus, demonstrating the long duration of action. The mean ejection fraction was not changed by bopindolol either at rest or after exercise but individual patients who responded to exercise with a fall in ejection fraction before treatment did not do so following treatment. These were mainly patients with 2 and 3 artery disease and the failure of the mean ejection fraction to show this protective effect was probably due to the predominance in our patients of those with mild single vessel disease who did not react adversely to exercise. We conclude that bopindolol protects the myocardium against ischaemia and that the effect lasts for at least 24 h when therapy is given once daily.

Acute and Long-Term Antihypertensive Effect of Bopindolol Once Daily or Once Weekly

Fourteen male patients, mean age 53 years (range 35-64), were included in an initial 3 months' double-blind crossover study, in which 1-2 mg bopindolol, a nonselective beta blocker with intrinsic sympathomimetic activity (ISA), was compared with 100-200 mg metoprolol regarding effects on blood pressure and heart rate. During the subsequent long-term therapy, eight patients were trained to measure home blood pressure, and in these patients bopindolol 1 mg daily was compared to 8 mg once weekly in a double-blind fashion for 3 weeks on each regimen. Bopindolol (mean dose 1.35 mg/day) caused a significant blood pressure reduction, 26/15 mm Hg, as did metoprolol, 24/3 mm Hg (mean dose 144 mg/day) (NS). Supine and standing heart rates were reduced during both bopindolol and metoprolol treatment. During long-term therapy with bopindolol satisfactory blood pressure control was achieved for 1 year in 11 patients. Heart rate was significantly reduced after 2-3 months' treatment and during the entire 1-year follow-up. Few and well-tolerated side effects were reported. During treatment with bopindolol 8 mg once weekly, the blood pressure control was maintained satisfactorily over the week and no significant differences were observed in comparison with daily administration (1 mg) of the drug.

Pharmacodynamic Models of Various β Blockers

Models describing the time course of effects (pharmacodynamic models) of various beta blockers in man are used to explain the long duration of action of bopindolol. No matter what effect is used [reduction in exercise heart rate (RER) or isoproterenol dose ratio (DR)] human data show clearly that bopindolol is very potent compared to other beta blockers such as atenolol, metoprolol, pindolol, practolol, and propranolol. In pharmacokinetic terms, however, these drugs show no pronounced difference in their elimination half-life (ranging between 4 and 8 h). Also the site of action of the therapeutic effects (beta 1 receptors) is obviously identical for all beta blockers. Furthermore, there is no evidence to suggest that bopindolol (the prodrug) or hydrolyzed bopindolol (the active substance) is further metabolized to a slowly eliminated active metabolite. Thus, drug disposition provides no argument to explain the long-lasting effects of bopindolol as compared other beta blockers. The long duration of action of bopindolol seems to reflect an usually flat plasma concentration-response curve.

Acute and long-term antihypertensive effect of bopindolol ? A nonselective ?-adrenergic blocker with ISA

14 male hypertensive patients, mean age 53 years first took part in a 3 month, double-blind crossover comparison of 1-2 mg bopindolol, a nonselective beta-blocker with ISA, and 100-200 mg metoprolol. Effects on blood pressure and heart rate were followed. One patient dropped out after the initial phase and the remaining 13 patients were followed for 1 year on bopindolol. 8 patients measured blood pressure at home, and in them bopindolol 1 mg o.d. and 8 mg once weekly were compared in a double-blind fashion, for 3 weeks on each regimen. Finally, after 1 year on bopindolol, treatment was withdrawn and blood pressure and heart rate were followed in 10 of the initial patients. Bopindolol in a mean dose of 1.35 mg/day caused a significant reduction in blood in pressure (26/15 mmHg), as did metoprolol (24/13 mmHg) in a mean dose of 144 mg/day. No significant difference in antihypertensive response was observed. Supine and standing heart rate were reduced both during bopindolol and metoprolol treatment. During long-term therapy with bopindolol, satisfactory blood pressure control was maintained up to 1 year in all patients, the average supine blood pressure being reduced from 173/107 to 144/90 mmHg. During treatment with bopindolol 8 mg once weekly, the blood pressure control was satisfactorily maintained over the week and no significant difference was observed in comparison with daily administration (1 mg) of the drug. When active treatment was withdrawn, a gradual increase in blood pressure and heart rate was observed, the pretreatment values being reached 8 weeks after discontinuation of bopindolol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)