SEARCH · PubMed Health

Results for “Celiprolol”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1996

Liquid chromatographic determination of total celiprolol or (S)-celiprolol and (R)-celiprolol simultaneously in human plasma.

A method has been developed for the determination of total celiprolol (sum of enantiomers) or the enantiomers (R)-celiprolol and (S)-celiprolol in plasma by high-performance liquid chromatography with UV and fluorescence detection. After extraction from alkalinized plasma with methyl-tert.-butyl ether and back-extraction into 0.01 M HCl (for total celiprolol determination) or after evaporation of the organic phase and derivatisation with R(-)-1-(1-naphthyl)ethyl isocyanate (enantiomer determination), total celiprolol or its diastereomeric derivatives were chromatographed on a reversed-phase HPLC column with a mixture of acetonitrile and phosphate buffer pH 3.5 (+0.05% triethylamine). Acebutolol was used as internal standard. Linearity was obtained in the range of 5 to 2000 ng/ml for total and 2.5 to 500 ng/ml for enantiomer determination. Intra-day and inter-day variation was lower than 10%. The method can be applied for analysis of plasma samples obtained from patients treated with oral racemic celiprolol doses.

Acebutolol↗

PubMed1990

[Pharmacological studies of celiprolol: III. Effects of celiprolol on the cardiovascular system and renal function, and its antiarrhythmic effects].

Effects of celiprolol on the cardiovascular system and renal function, and its antiarrhythmic effects were studied. 1. In anesthetized dogs, celiprolol (0.01-3 mg/kg, i.v.) dose-dependently depressed the maximum rate of rise of left ventricular pressure, cardiac output and cardiac work less severely than propranolol and atenolol. 2. Celiprolol (0.01 mg/kg, i.v.) decreased the myocardial oxygen consumption in anesthetized dogs as potently as propranolol. 3. Celiprolol (0.03-3 mg/kg, i.v.) tended to increase femoral blood flow. Celiprolol (1 mg/kg, i.v.) increased common carotid blood flow. 4. Celiprolol decreased urine volume and urinary excretion of Na+ and Cl- at doses of 1 and 10 mg/kg and increased the sodium reabsorption rate at a dose of 10 mg/kg in anesthetized dogs, whereas it produced no change in plasma renin activity. 5. Celiprolol inhibited both halothane-adrenaline arrhythmia in dogs and ouabain-induced arrhythmia in rabbits. Its antiarrhythmic effects were 1/10-1/3 as potent as those of propranolol. 6. Celiprolol suppressed the maximum rate of rise of action potential at a concentration of 3 x 10(-4) M, which was 30 times as high as that of propranolol. Celiprolol (3 x 10(-5)-3 x 10(-4) M) dose-dependently shortened the effective refractory period (ERP), but it produced no change in the ratio of ERP to action potential duration. 7. These results suggest that celiprolol may be a useful drug for the treatment of ischemic heart disease and some types of arrhythmia, and that it has only a little influence on renal function.

Action Potentials↗

PubMed1991

Comparison of celiprolol and propranolol in stable angina pectoris. Celiprolol International Angina Study Group.

The comparative antianginal effects and safety of propranolol and celiprolol, a highly beta 1-selective adrenoceptor blocker with selective partial beta 2-adrenoceptor agonist activity, were assessed in an international multicenter, placebo run-in, active control, double-blind, randomized, titration-to-effect study of 140 patients with stable, exercise-induced angina pectoris. At baseline, all patients received placebo for 2 weeks, then titrated doses of once-daily celiprolol (200, 400, 600 mg) or twice-daily propranolol (total daily dose 80, 160, 320 mg) over 4 weeks, followed by a 2-week maintenance period. Heart rate and blood pressure, at rest and with exercise, weekly anginal attack frequency, nitroglycerin consumption and symptom-limited treadmill exercise times (modified Bruce protocol) were assessed. Compared with their respective baselines, both celiprolol and propranolol reduced anginal attack and nitroglycerin consumption rates to a comparable degree, while improving exercise tolerance (p less than 0.05). Treatment with propranolol compared with celiprolol, however, was associated with a significantly lower heart rate at rest (p less than 0.01). The double-product at the conclusion of exercise testing was significantly reduced by both drugs. Celiprolol and propranolol had similar effects on blood pressure, and were well tolerated. More symptomatic bradycardia occurred with propranolol. Despite the differences in their hemodynamic actions, once-daily celiprolol is as effective as twice-daily propranolol in the treatment of patients with stable angina pectoris.

Adrenergic beta-Antagonists↗

PubMed2000

Long-term celiprolol therapy lowers fasting plasma leptin levels. Celiprolol Multicenter Study Group.

The effects of celiprolol on fasting plasma leptin levels, glucose tolerance, and insulin sensitivity were studied in a randomized, investigator-masked, and parallel clinical trial. Modified oral glucose tolerance tests (OGTT) were performed during the previous antihypertensive monotherapy (beta- or Ca-blocker, or ACE inhibitor), and 6 and 12 months after randomization to celiprolol (200-400 mg daily) or to control group, where the therapy was kept unchanged. One hundred sixty-nine dyslipidemic and hypertensive nondiabetics with an age range of 42-65 years and an average body mass index of 28.4 kg/m2 completed the study according to the protocol. The mean circulating leptin level decreased from 7.5 to 6.6 ng/mL in men (p < 0.05) and from 23.0 to 19.7 ng/mL in women during the 12-month celiprolol treatment. The incremental glucose area under the curve (AUC) in the 2-hour OGTT decreased from 3.8 to 3.0 h* mmol/L (p < 0.01), and insulin AUC decreased from 134 to 99 h* mU/L (p < 0.01). The insulin sensitivity index increased by 22% (p < 0.01) and the serum triglyceride level decreased by 15% in the celiprolol group. Changes in serum cholesterol were clinically insignificant. In the control group, no significant change was seen in any measured variable. A decrease in leptin levels in the celiprolol group was associated with improved insulin sensitivity, while the weight of the moderately obese patients did not change. The clinical significance of a 14% decrease in fasting plasma leptin level remains to be elucidated. The results suggest amelioration of leptin resistance during long-term celiprolol therapy.

Adrenergic beta-Antagonists↗

PubMed1990

[Pharmacological studies of celiprolol: II. Alpha 2-Adrenoceptor blocking effects of a cardioselective beta-blocker, celiprolol].

alpha-Adrenoceptor blocking effects of the cardioselective beta-blocker celiprolol were tested. 1. Celiprolol antagonized the contractions induced by UK-14304, but not those by phenylephrine, in isolated rat tail arteries with a pA2 value of 4.95. 2. In the isolated rat vas deferens, twitch contractions elicited by the transmural electrical stimulation (TS) were almost blocked by TTX (10(-7) M). Clonidine inhibited the TTX-sensitive contraction in a concentration-dependent manner. Celiprolol produced little effect on the inhibitory effects of clonidine. The concentration-inhibition curve of clonidine was shifted to the right by yohimbine (10(-8) M), but not by prazosin (10(-8) M). 3. Although celiprolol slightly increased the 3H-efflux to TS from the [3H]-norepinephrine-loaded rat vas deferens, the increment was not significant. Yohimbine (10(-7) M) significantly increased the 3H-efflux. TTX (10(-7) M) and bretylium (3 x 10(-5) M) blocked the 3H-efflux. 4. In the spinal rat treated with propranolol (3 mg/kg, i.v.) and prazosin (0.1 mg/kg, i.v.), celiprolol (30 and 100 mg/kg, i.v.) and yohimbine (0.1-1 mg/kg, i.v.) inhibited the pressor response to clonidine. 5. These results indicate that celiprolol may have a weak alpha 2-blocking effect which was more effective on postsynaptic alpha 2-receptors than presynaptic ones.

Adrenergic alpha-Antagonists↗

PubMed1989

[The results of a celiprolol drug surveillance study in Spain. The Celiprolol Multicenter Group].

The aim of this prospective multicenter study is to determine the efficacy and tolerance of a new, highly cardioselective beta-blocking agent with vasodilatation effects, Celiprolol. 185 patients with mild-light blood hypertension, grade 1-2, were admitted. Patient's progress was followed in 21 centers, 15 of them not being evaluated due to study protocol transgression. 82 patients were male and 87 female, with a median age of 50 +/- 11 (18-74). A doses of 200 mq/day of Celiprolol, once a day, during 2 weeks produced a significant statistical decrease of TAS and TAD (165 +/- 18 vs 151 +/- 18 mmHg, P less than 0.01 and 103.9 +/- 7 vs 94 +/- 9, P less than 0.01), with a minimal reduction of CR (78.5 +/- 10 vs 72.9 +/- 8 p min); 72 patients (43%) did not show a decrease in TAD lower than 95 mmHg, this being the reason to increase the celiprolol doses to 400 mg once a day, obtaining a decrease of TAS and TAD (TAS 146 +/- 16, P less than and TAD 90.5 +/- 9, P less than 0.01) with final CR of 71 +/- 8 p min. 18 patients had secondary effects, being mild in 16 cases, moderate in 2 and only one left the study spontaneously. 107 patients obtained a good control of blood hypertension (TAD less than 90) (62.9%), 80 of them with 200 mg doses. Analysing quality of life, 97 patients recognised that they left better (59.9%), 58 (35.8%) no different, and only 7 (4.3%) worse.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1985

[Intrinsic sympathomimetic action and its special features as demonstrated by the beta-1-receptor blocker celiprolol].

The Intrinsic Sympathetic Activity (ISA) of the beta-1-adrenoceptor blocker celiprolol was tested in a series of pharmacological and clinical investigations. Celiprolol shows much more pronounced positive chronotropic effects in spontaneously beating atria of cats than in those of guinea-pigs and rats. Positive inotropic effects of celiprolol are much pronounced in the left kitten atrium, but scarcely demonstrable in the kitten papillary muscle. Celiprolol has no influence on the adenylyl cyclase activity of the dog heart. In reserpinized rats and reserpinized, adrenalectomized, vagotomized cats celiprolol increases the heart rate to the same extent as the beta-blocker pindolol. In ganglion-blocked dogs celiprolol distinctly increases heart rate and left ventricular contraction force. Celiprolol relaxes isolated human arterial and venous strips and induces a transient increase of the femoral arterial blood flow in anaesthetized dogs. Celiprolol relaxes isolated bovine tracheal muscle preparations and reduces the airway resistance in anaesthetized cats infused with serotonin. The intrinsic chronotropic effects of celiprolol in cat atria in vitro and in reserpinized rats in vivo and the relaxing effects of celiprolol in isolated bovine tracheal muscles are antagonized by propranolol, and therefore these actions may be explained by the ISA of celiprolol. However the vascular relaxing effects of celiprolol in vitro and in vivo and the bronchodilating effects in the serotonin-infused cat are not blocked by propranolol. In order to obtain a more precise characterization of these surprising effects, further pharmacological investigations were done. In the isolated femoral artery of the dog the concentration-response curve of calcium chloride is not influenced by celiprolol while it is antagonized by verapamil. A serotonin antagonistic effect cannot be demonstrated for celiprolol either in receptor binding studies or on the blood pressure of anaesthetized dogs. Celiprolol inhibits the methacholine bronchospasm in rats and the prostaglandin F2 alpha-induced bronchoconstriction in cats. The histamine-induced bronchoconstriction in dogs is scarcely affected by celiprolol while it is enhanced by propranolol. In radioligand studies celiprolol shows a tenfold higher affinity for alpha-2 in comparison to alpha-1 receptors. Celiprolol enhances the inhibitory effect of clonidine in the electrically stimulated vas deferens of the rat in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic beta-Antagonists↗

PubMed2003

Itraconazole increases but grapefruit juice greatly decreases plasma concentrations of celiprolol.

OBJECTIVES: Our objective was to evaluate the effects of itraconazole and grapefruit juice on the pharmacokinetics of the beta-adrenergic receptor-blocking agent celiprolol in healthy volunteers. METHODS: In a randomized 3-phase crossover study, 12 healthy volunteers took itraconazole 200 mg orally or placebo twice a day or 200 mL grapefruit juice 3 times a day for 2 days. On the morning of day 3, 1 hour after ingestion of itraconazole, placebo, or grapefruit juice, each subject ingested 100 mg celiprolol with 200 mL of water (placebo and itraconazole phases) or grapefruit juice. In addition, 200 mL of water or grapefruit juice was ingested 4 and 10 hours after celiprolol intake. The plasma concentrations of celiprolol, itraconazole, and hydroxyitraconazole and the excretion of celiprolol into urine were measured up to 33 hours after dosing. Systolic and diastolic blood pressures and heart rate were recorded with subjects in a sitting position before the administration of celiprolol and 2, 4, 6, and 10 hours later. RESULTS: During the itraconazole phase, the mean area under the plasma concentration-time curve from 0 to 33 hours [AUC(0-33)] of celiprolol was 80% greater (P <.05) than in the placebo phase. During the grapefruit juice phase, the mean AUC(0-33) and peak plasma concentration values of celiprolol were reduced to about 13% (P <.001) and 5% (P <.001) of the respective placebo phase values. The cumulative excretion into urine of celiprolol was increased by 59% by itraconazole (P <.05) and decreased by 85% by grapefruit juice (P <.001). Hemodynamic variables did not differ between the phases. CONCLUSIONS: Itraconazole almost doubles but grapefruit juice greatly reduces plasma concentrations of celiprolol. The itraconazole-celiprolol interaction most likely resulted from increased absorption of celiprolol possibly as a result of P-glycoprotein inhibition in the intestine. The reduced celiprolol concentrations during the grapefruit juice phase were probably caused by physicochemical factors that interfered with celiprolol absorption, although other mechanisms cannot be excluded. The grapefruit juice-celiprolol interaction is probably of clinical relevance.

Administration, Oral↗

PubMed1997

Celiprolol: agonist and antagonist effects at cardiac beta 1- and vascular beta 2-adrenoceptors determined under in vivo conditions in the rat.

Celiprolol is a beta-adrenoceptor antagonist which has desirable ancillary properties since it is relatively cardioselective and can exert direct vasodilator and bronchodilator effects. Here agonist and antagonist effects of celiprolol at cardiac beta 1- and vascular beta 2-adrenoceptors were determined under in vivo conditions in the rat. All experiments were carried out in catecholamine-depleted, pentobarbital anesthetized and vagotomized rats, placed under artificial respiration. I.v. administrations were made via the femoral vein. Blood pressure was measured from the cannulated right carotid artery and heart rate was recorded with a cardiotachometer. Celiprolol (10 micrograms/kg to 1 mg/kg i.v.) produced dose-related increases in heart rate and decreases in mean carotid artery blood pressure which were of longer duration than those mediated by standard agonists of beta 1-(isoprenaline) or beta 2-(salbutamol) adrenoceptors respectively. Although the maximal increase in heart rate by celiprolol (110 +/- 4 beats/min, n = 7) was approximately half that of isoprenaline (198 +/- 1 beats/min, n = 5), isoprenaline acted at doses 200-fold lower than celiprolol. Betaxolol (0.03-0.3 mg/kg i.v.), a beta 1-adrenoceptor antagonist, inhibited strongly and with similar potency the tachycardiac effects of celiprolol (DR10 = 45 micrograms/kg i.v.) as well as isoprenaline (DR10 = 45 micrograms/kg i.v.). On the other hand, the hypotensive effects of celiprolol and salbutamol were antagonized markedly and with similar potency by ICI 118,551, a relatively selective beta 2-adrenoceptor antagonist (DR10 = 15 and 25 micrograms/kg i.v. respectively). In rats pretreated with celiprolol (0.03 to 0.3 mg/kg i.v.), the heart rate dose-response curves to isoprenaline were shifted to the right of those determined in matched groups of vehicle-pretreated animals. In this respect, celiprolol was half as potent as betaxolol in blocking cardiac beta 1-adrenoceptors. Furthermore, celiprolol also antagonized the hypotensive effects of salbutamol, but, in this respect, celiprolol was 90-fold less potent than ICI 118,551. In conclusion, these results clearly indicate that celiprolol has the ability of stimulating and blocking not only cardiac beta 1- but also vascular beta 2-adrenoceptors. The effects on cardiac beta 1-adrenoceptors as well as the agonism of beta 2-adrenoceptors are produced by similar doses of celiprolol. These doses are notably lower than those necessary to block beta 2-adrenoceptors. Thus, this pharmacological profile, which has also been demonstrated in humans, indicates that celiprolol is a modulator of cardiac beta 1-adrenoceptors with vascular beta 2-adrenoceptor agonist properties.

Adrenergic beta-Agonists↗

PubMed2003

Rifampicin reduces plasma concentrations of celiprolol.

OBJECTIVE: The beta-adrenoceptor-blocking agent celiprolol undergoes negligible metabolism, but is a substrate for P-glycoprotein. Our objective was to investigate the effects of rifampicin on the pharmacokinetics of celiprolol in healthy subjects. METHODS: In a randomized cross-over study with two phases and a washout of 4 weeks, ten healthy volunteers received a 5-day pretreatment with rifampicin (600 mg daily) or placebo. On day 6, a single 200-mg dose of celiprolol was administered orally. The plasma concentrations of celiprolol and the excretion of celiprolol into urine were measured up to 33 h after its dosing. Systolic and diastolic blood pressures and heart rate were recorded in a sitting position before the administration of celiprolol and 2, 4, 6, and 10 h later. MDR1 (P-glycoprotein) genotype was assessed with respect to polymorphisms in exon 21 (G2677T/A) and in exon 26 (C3435T). RESULTS: Rifampicin pretreatment reduced the median area under the plasma celiprolol concentration-time curve AUC(0-33 h) to 0.44-fold [90% confidence interval (CI), 0.27-0.86], relative to the placebo. The median peak plasma concentration, the time of peak concentration, and the elimination half-life of celiprolol were not significantly changed by rifampicin. During the rifampicin phase, the median amount of celiprolol excreted into urine was decreased by 47% ( P<0.05) and celiprolol renal clearance increased by 19% ( P<0.05) compared with the placebo phase. There were great inter-individual differences in the extent of rifampicin-celiprolol interaction. However, no association was found between the MDR1 polymorphisms and the degree of interaction between rifampicin and celiprolol. No significant differences were observed in hemodynamic parameters between the phases. CONCLUSION: Rifampicin pretreatment reduces plasma celiprolol concentrations, possibly by induction of the efflux transporter P-glycoprotein, particularly in the intestinal wall, which leads to decreased absorption of celiprolol.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1984

Effects of celiprolol (REV 5320), a new cardioselective beta-adrenoceptor antagonist, on in vitro adenylate cyclase, alpha- and beta-adrenergic receptor binding and lipolysis.

Celiprolol has been previously shown in vivo to be an effective beta-adrenergic antagonist with cardio-selectivity and weak intrinsic sympathomimetic activity but no membrane stabilizing or "quinidine-like" effects. With in vitro systems reported here, the following was observed. Against the stimulation of adenylate cyclase from dog ventricular muscle by isoproterenol, celiprolol had a Ki of 2.6 X 10(-7) M which was about 1/20 the potency of propranolol. At 100 microM, celiprolol did not affect histamine or dopamine concentration-response curves for the stimulation of adenylate cyclase from guinea-pig cerebral cortex. By itself, up to 1 mM, celiprolol did not affect basal adenylate cyclase activity from either preparation. With in vitro radioligand binding assays to directly measure beta-adrenergic receptor interactions, celiprolol had Ki values of 1.4 X 10(-7) to 8.3 X 10(-6) M. A 35-fold beta selectivity was noted with membranes from rat heart vs. rat reticulocytes, which supports previously reported in vivo data on cardioselectivity. No difference in affinity to beta-receptors was noted with frog vs. turkey erythrocyte membranes which supports the contention that these two non-mammalian systems are not predictive of beta1/beta2 specificity with mammalian systems. Celiprolol also showed some selective alpha2-adrenoceptor antagonism against (3H)-yohimbine binding vs. (3H)-prazosin binding to membranes from rat cerebral cortex. With rat adipocytes, up to 300 microM celiprolol did not stimulate basal lipolysis in the presence or absence of 10 microM 1-methyl-3-isobutyl-xanthine. Celiprolol inhibited isoproterenol-induced lipolysis with a potency about 2 times greater than practolol. Unlike propranolol, celiprolol at very high concentrations did not show non-specific inhibition of lipolysis induced with cyclic nucleotides. These and other published data would suggest the following: in vitro beta adrenergic receptor antagonist activity can be demonstrated for celiprolol, cardioselectivity is due to a combination of many factors including stereochemistry of the molecule and in vivo distribution and metabolism, celiprolol does not possess "non-specific" membrane activity, the "intrinsic-sympathomimetic activity" of celiprolol is selectively observed in some but not all in vitro test models, celiprolol has about a 10-fold selectivity for alpha 2-vs. alpha 1-receptors which is relatively unique to beta-antagonists and needs further investigations as to the potential physiological significance.

Adenylyl Cyclases↗

PubMed2004

Orange juice substantially reduces the bioavailability of the beta-adrenergic-blocking agent celiprolol.

BACKGROUND: Grapefruit juice was recently found to decrease plasma concentrations of the beta-adrenergic receptor-blocking agent celiprolol. Our objective was to investigate the effect of orange juice on the pharmacokinetics of celiprolol in healthy subjects. METHODS: In a randomized crossover study with 2 phases and a washout of 2 weeks, 10 healthy volunteers ingested either 200 mL normal-strength orange juice or water 3 times a day for 2 days. On the morning of day 3, 1 hour after ingestion of 200 mL orange juice or water, each subject ingested 100 mg celiprolol with either 200 mL orange juice or water. In addition, 200 mL orange juice or water was ingested at 4, 10, 22, and 27 hours after celiprolol intake. The concentrations of celiprolol in plasma and its excretion into urine were measured up to 33 hours after its dosing. Systolic and diastolic blood pressures and heart rate were recorded up to 10 hours. RESULTS: Orange juice reduced the mean peak plasma concentration of celiprolol by 89% (P <.01) and the mean area under the plasma celiprolol concentration-time curve by 83% (P <.01). The time to peak concentration of celiprolol increased from 4 to 6 hours (P <.05), and the half-life was prolonged from 4.6 to 10.8 hours (P =.05) after ingestion of orange juice. Orange juice reduced the urinary excretion of celiprolol by 77% (P <.01). No significant differences were observed in the hemodynamic variables between the phases. CONCLUSIONS: Orange juice substantially reduces the bioavailability of celiprolol, but the mechanism of this interaction remains to be resolved. For example, modulation of intestinal pH and of function of transporters implicated in the absorption of celiprolol may be involved. Because of the great extent of the orange juice-celiprolol interaction and a wide use of orange juice, this interaction is likely to have clinical importance in some patients, although hemodynamic consequences were not seen in young healthy subjects.

Adrenergic beta-Antagonists↗

PubMed2000

Treatment of heart failure with celiprolol, a cardioselective beta blocker with beta-2 agonist vasodilatory properties. The CELICARD Group.

Treatment with beta blockers results in improvement in functional status, and reduces mortality in patients with heart failure. A number of differences in the results noted could be due to additional properties of the specific beta blockers studied: absence of cardioselectivity, and existence of a vasodilator effect and of an associated antioxidant effect. We studied the effects of celiprolol, a cardioselective beta blocker with a stimulant effect on beta2 receptors. One hundred thirty-two patients presenting with chronic heart failure of various etiologies, with an ejection fraction of <40% and New York Heart Association cardiac functional status grades II and III were included in a randomized, double-blind, placebo-controlled study. The maximum dose of celiprolol (100 mg) was attained after 1 month. The study lasted 1 year. The primary evaluation criterion was functional class as evaluated using the Goldman questionnaire. There was no difference in efficacy between the 2 treatment groups in terms of functional class (p = 0.56). With regard to the secondary evaluation criteria, an improvement in DiBianco functional score was seen with celiprolol (p = 0.03), as well as a significant reduction in heart rate (p = 0.01). Ejection fraction increased in both groups (p = 0.15). There was no difference regarding improvement in left ventricular volume as determined at echocardiography or in exercise capacity. The safety profile of celiprolol was excellent. There was no difference in terms of cardiovascular mortality (2 receiving celiprolol vs 4 placebo), onset of arrhythmias (2 receiving celiprolol vs 3 placebo), worsening of heart failure (26 receiving celiprolol vs 23 placebo), or noncardiovascular adverse events (9 receiving celiprolol vs 14 placebo). The absence of a significant efficacy of celiprolol, a beta blocker with vasodilator properties, but exerting stimulation of beta2 receptors, suggests an unfavorable role of this latter property in heart failure. However, the safety profile of celiprolol was excellent. This beta blocker may consequently be used for its other indications, hypertension and angina, in patients presenting with altered cardiac function.

Adrenergic beta-Antagonists↗

PubMed2000

Effect of atenolol and celiprolol on acetylcholine-induced coronary vasomotion in coronary artery disease.

Earlier studies have reported on the potentiated muscarinic vasoconstriction of intracoronary acetylcholine after metoprolol application in patients with coronary artery disease. The present study investigated the effect of celiprolol, atenolol, and placebo on acetylcholine-induced vasomotion in patients with coronary artery disease. Furthermore, direct effects on coronary vasomotion and on hemodynamics were evaluated. Acetylcholine (intracoronary concentrations of 6.3x10(-7), 2.0x10(-6), and 6.3x10(-6) M) was given before and after double-blind celiprolol (0.30 mg/kg IV), atenolol (0.15 mg/kg IV), or placebo in 3x12 patients. Vasomotion was investigated by quantitative coronary angiography in proximal and distal segments of epicardial coronary arteries, and by the determination of the coronary resistance index based on Doppler-flow measurements. The investigated drugs had no direct affect on the diameter of the epicardial coronary arteries. However, celiprolol, in contrast to atenolol, significantly reduced systemic vascular resistance (change after atenolol: from 1,855+/-308 to 2,161+/-550 dyne s cm(-5); celiprolol: 1,691+/-435 to 1,411+/-343 dyne s cm(-5); and placebo: 1,722+/-215 to 1,710+/-213 dyne s cm(-5), p<0.001) and the coronary resistance index (change after atenolol: 2.52+/-3.58 to 2.86+/-4.24; celiprolol: 2.70+/-1.55 to 2.49+/-2.26; and placebo: 1.97+/-1.35 to 1.92+/-1.25, p<0.01). Celiprolol, atenolol, and placebo did not have different effects on acetylcholine-induced coronary vasomotion of epicardial conductance vessels (diminution of proximal lumen diameter before/after atenolol: 0.42+/-0.39/0.44+/-0.39 mm; celiprolol: 0.32+/-0.26/0.30+/-0.24 mm; and placebo: 0.36+/-0.29/0.43+/-0.40 mm) and of coronary resistance vessels (reduction of coronary resistance index before/after atenolol: 1.95 +/-4.74/ 1.92+/-3.74; celiprolol: 0.98+/-0.73/1.41+/-1.50; and placebo: 1.16+/-1.29/1.16+/-1.04). In contrast to atenolol, celiprolol possesses vasodilative properties in systemic and coronary resistance vessels. There was no direct effect on the diameter of conductance vessels. Acetylcholine-induced coronary vasomotion both in conductance and resistance vessels was not influenced by the beta blockers that were studied. This suggests that atenolol and celiprolol do not influence endothelium-dependent, nitric oxide related vasomotion.

Acetylcholine↗

PubMed1987

No evidence for a direct vasodilatory effect of celiprolol on human vasculature in vivo or in vitro.

Celiprolol is reported to be a new cardioselective beta blocker with novel ancillary properties including vasodilator effects. The purpose of this study was to investigate whether celiprolol possesses a direct vasodilatory effect on human vasculature in vivo and in vitro. We studied the in vivo effects of intra-arterial celiprolol (1-100 micrograms/min i.a.) on forearm blood flow (FBF). Forearm blood was measured by venous occlusion plethysmography. Possible vasorelaxant actions of celiprolol on human vascular smooth muscle were studied using segments of isolated human saphenous vein in vitro. The effect of celiprolol was investigated on resting tone or noradrenaline induced tone. Possible alpha 2-adrenoceptor antagonist effects of celiprolol were assessed using celiprolol as an antagonist of BHT933 induced constriction. Celiprolol was without significant effect on FBF and failed to relax isolated saphenous vein segments preconstricted with noradrenaline. The weak alpha 2-adrenoceptor antagonist action of celiprolol was demonstrable in human saphenous vein. This study does not provide evidence for a direct vasodilatory effect of celiprolol on human vasculature.

Adrenergic beta-Antagonists↗

PubMed1988

Celiprolol--overview of 6 years of clinical trials experience.

The results of an extensive pre-clinical and clinical research programme indicate that celiprolol is a safe and effective treatment for both hypertension and angina pectoris. Celiprolol is well absorbed, is largely unmetabolized, and is excreted equally in the urine and bile. As a result of this pharmacokinetic profile celiprolol can be safely administered to the elderly and to patients with renal or hepatic impairment. Haemodynamic studies indicate that celiprolol lowers arterial blood pressure, and decreases both renal vascular resistance and peripheral vascular resistance. Celiprolol does not depress myocardial function, neither does it induce bronchoconstriction in asthmatic patients. Weak alpha 2-adrenoceptor antagonism, combined with beta 2-adrenoceptor agonism are thought to contribute to these properties. The antihypertensive efficacy of celiprolol, 200 mg/day, is comparable to that of propranolol, atenolol and nadolol. Moreover, the actions of celiprolol last for 24 h, and are accompanied by less resting bradycardia than that seen with other beta-blockers. The anti-anginal efficacy of celiprolol is similar to that of atenolol, propranolol and metoprolol. In addition, celiprolol decreases the ventricular rate in patients with atrial tachyarrhythmias. This effect results from its ability to slow atrioventricular conduction. Celiprolol is generally very well tolerated.

Adrenergic beta-Antagonists↗

PubMed1991

The effect of celiprolol on the blood lipid profile in hypertensive patients with high cholesterol levels.

The aim of this study was to compare the effects of chronic antihypertensive therapy with either celiprolol or atenolol on plasma lipids in patients with hypercholesterolemia. Forty-six patients with essential hypertension and a total cholesterol (TC) concentration greater than 220 mg/dl were studied. After 1 month on placebo, patients were stratified into five classes on the basis of their plasma TC levels and then randomized to receive atenolol 100 mg/day or celiprolol 400 mg/day for 1 year. Blood pressure (BP), heart rate (HR), and blood samples for evaluation of TC, HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), and triglycerides (TG) were taken before and after the placebo period, and every 6 months from the beginning of the active treatment. Celiprolol and atenolol caused similar reduction in BP. Both atenolol and celiprolol decreased TC. Atenolol significantly reduced HDL-C, while celiprolol increased it (p less than 0.01 at 12 months), and the difference between the two drugs was statistically significant in this regard. LDL-C levels were not significantly affected by atenolol, but were progressively reduced by celiprolol (p less than 0.05 at 6 months, p less than 0.01 at 12 months). TG rose under atenolol but was reduced by celiprolol (p less than 0.05). The results of this study show that the celiprolol-induced changes in plasma lipids may be favorable and suggest that, in hypertensive patients with high cholesterol levels, beta-blocker therapy with celiprolol may be effective in lowering BP without worsening the lipid profile.

Adult↗

PubMed1995

Interactions of a new beta-blocker, celiprolol, with the calcium antagonists, diltiazem and nifedipine, on atrioventricular conduction.

The influence of a new beta-blocker, celiprolol, on the direct dromotropic effects of the Ca antagonists, diltiazem and nifedipine, on atrioventricular (AV) conduction was estimated in the canine isolated, blood-perfused AV node preparation. Diltiazem (1-10 micrograms) and nifedipine (0.3-3 micrograms) injected i.a. into the AV node artery dose dependently prolonged the atrio-His (AH) interval (5-39 msec and 7-51 msec) in the AV mode preparation. When celiprolol (1 and 10 mg/kg) was given i.v. in the support dog, the AH interval in the AV node preparation was transiently shortened and then maintained constant as a control. These doses of i.v. celiprolol completely abolished the isoproterenol-induced decrease in the AH interval (28 msec at 0.03 microgram, i.a.) and AV nodal tachycardia. In the presence of celiprolol, the same doses of i.a. diltiazem and nifedipine increased the AH interval by the same amounts (6-43 msec and 8-53 msec) as the control. The incidence of second degree AV conduction block produced by diltiazem (2 in 5 AV node preparations at 10 micrograms) and nifedipine (2 in 6 preparations at 3 micrograms) was not changed by celiprolol. In the second experiments, diltiazem (30-300 micrograms/kg) and nifedipine (3-30 micrograms/kg), given i.v. in an open-chest in situ vagotomized dog, dose dependently increased AV conduction time (AVCT; 2-30 msec and 1-12 msec). Celiprolol 1 and 10 mg/kg i.v., which suppressed the isoproterenol-induced decrease in AVCT (32 msec at 0.3 mu/kg i.v.) and AV nodal tachycardia (4 in 6 in situ hearts), potentiated the prolongation of AVCT by the same doses of diltiazem (11-50 msec) and nifedipine (3-40 msec). The incidence of second degree AV conduction block produced by i.v., diltiazem (1 in 5 in situ hearts at 300 micrograms/kg) and nifedipine (0 in 6 in situ hearts at 30 micrograms/kg) was aggravated (4 in 5 and 3 in 6 in situ hearts) after i.v. celiprolol. These results indicate that although celiprolol does not affect the direct negative dromotropic effects of the Ca antagonists, AV block could easily be produced when celiprolol eliminates tonic adrenergic influences in vivo.

Adrenergic beta-Antagonists↗