Haemodynamic effects in man during exercise of a single oral dose of narbivolol (R 67555), a new beta‐1‐adrenoceptor blocking agent: A comparative study with atenolol, pindolol, and propranolol

Abstract

De Cree, J., H. Geukens, J. Leempoels, and H. Verhaegen: Haemodynamic effects in man during exercise of a single oral dose of narbivolol (R 67555), a new beta-l-adrenoceptor blocking agent: A comparative study with atenolol, pindolol, and propranolol. Drug Dev. Res. 8:109-117, 1986.In eight normal volunteers R 67555 at 5 mg and 10 mg significantly lowered the exerciseinduced increase of systolic blood pressure by 20 and 25%, and the exercise-induced increase of heart rate by 20 and 21% respectively. The blood pressure lowering effect of R 67555 6 hr after intake was comparable to that observed after atenolol, pindolol, and propranolol. In contrast, the lowering of exercise-induced increase of heart rate was significantly less with R 67555 than with the other beta-blockers tested. The ratio of PEP,/ LVET,, a measure of left ventricular performance, significantly increased 3 hr after intake of atenolol, propranolol, and 10 mg of R 67555 but not after pindolol and 5 mg of R 67555. Six hr after administration of pindolol and of 5 mg of R 67555, the ratio PEPdLVET, was significantly lowered as compared with control values. The post-exercise left ventricular ejection time (LVET,) significantly shortened 3 hr and 6 hr after intake of 5 mg and 10 mg of R 67555, whereas a trend to prolongation was observed after administration of atenolol, pindolol, and propranolol.

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

“…Nebivolol ( 1 , Fig. 1) is a chroman-based antihypertensive drug that was first reported in the racemic form [2–3]. Chiral HPLC was subsequently employed to access various stereoisomers of 1 in enantiomerically pure form [4–5].…”

“…Out of the ten possible stereoisomers of 1 , ( S , R , R , R )-nebivolol or (+)-nebivolol ( 1a , Fig. 1) was found to be a potent β 1 -adrenergic receptor blocker [2–3]. On the other hand, the corresponding enantiomeric form, ( R , S , S , S )-nebivolol or (−)-nebivolol ( 1b , Fig.…”

A Thiophene-2-carboxamide-Functionalized Zr(IV) Organic Framework as a Prolific and Recyclable Heterogeneous Catalyst for Regioselective Ring Opening of Epoxides

“…Renin and HIV-1 protein inhibitors constitute pharmacologically active amino alcohols, and one such example is saquinavir . Often, β-adrenergic blockers, which constitute a class of β-amino alcohols, are used to regulate cardiovascular diseases such as hypertension, cardiac arrhythmias, and angina pectoris. − Ring opening of oxiranes by nucleophilic attack of various amines is the easiest way to prepare β-amino alcohols. , However, this approach is not acceptable due to its disadvantages such as the sluggish reaction rate because of the sensitivity of epoxides and decrease in regioselectivity. There are many reports involving the preparation of β-amino alcohols utilizing epoxides as electrophiles. ,− Researchers have designed several routes such as the use of homogeneous catalysts, , alumina, alkali metals, metal amides, and silica gel in order to increase the electrophilicity of epoxides.…”

Heterogeneous catalysis of novel polymeric rare earth complexes under solvent-free conditions: Zero-emission synthesis of β-amino alcohols

“…␤-Amino alcohols are versatile synthetic intermediates for a wide rage of biologically active natural and unnatural products [4][5][6]. They can also serve as good chiral ligands of some asymmetric metal complex catalysts [7].…”