Article: Different pharmacological properties of two enantiomers in a unique beta-blocker, nebivolol.
2008 Volume 26, Issue 2, Page(s) 115–134
Abstract: Nebivolol is a racemic combination of d-nebivolol (+SRRR nebivolol) and l-nebivolol (-RSSS ... developing from a central nitrogen atom. D-nebivolol and l-nebivolol divaricate pharmacologically and ... of the l-enantiomer, which in itself does not influence systolic and diastolic blood pressure. Furthermore ...
| Abstract | Nebivolol is a racemic combination of d-nebivolol (+SRRR nebivolol) and l-nebivolol (-RSSS nebivolol) that differs chemically from other beta-blockers, with an absolutely symmetrical configuration developing from a central nitrogen atom. D-nebivolol and l-nebivolol divaricate pharmacologically and therapeutically, with a noticeably different profile from that of conventional beta-blockers; for instance, the selective blocking of beta(1)-adrenoceptors is determined almost exclusively by d-nebivolol. Both enantiomers act synergistically with respect to blood pressure reduction: the effect of nebivolol on heart rate is exclusively exerted by d-nebivolol, with these hypotensive effects enhanced by the addition of the l-enantiomer, which in itself does not influence systolic and diastolic blood pressure. Furthermore, this pronounced and lasting blood pressure reduction is roughly equal to the effect of conventional beta-blockers in high doses. In certain vascular districts, nebivolol stimulates endothelial nitric oxide (NO) synthesis, thereby increasing the availability of NO in the endothelium, smooth muscle, and platelets and, consequently, producing a sustained vasodilation, with decreases in peripheral resistance and blood pressure. These effects are not shared by other beta-adrenoceptor blockers used as references and mainly rely on the l-enantiomer. L-nebivolol also increases NO availability under conditions of oxidative stress by the inhibition of endothelial NO synthase (eNOS) uncoupling, thereby reducing NO inactivation. Furthermore, neither nebivolol nor its enantiomers show any intrinsic sympathomimetic activity and undesirable beta-blocker effects, such as a decrease in cardiac output, which do not occur or are less pronounced with the combination of d-nebivolol and l-nebivolol. In conclusion, the independent pharmacologic and clinical effects of d-nebivolol and l-nebivolol act synergistically to produce a cardiovascular profile that differs noticeably from that of conventional beta-blockers. |
|---|---|
| MeSH term(s) | Adrenergic beta-1 Receptor Antagonists ; Adrenergic beta-Antagonists/pharmacology ; Animals ; Benzopyrans/pharmacology ; Blood Platelets/drug effects ; Blood Platelets/metabolism ; Blood Pressure/drug effects ; Dose-Response Relationship, Drug ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; Ethanolamines/pharmacology ; Heart Rate/drug effects ; Hemodynamics/drug effects ; Humans ; Isomerism ; Molecular Structure ; Myocardial Contraction/drug effects ; Nebivolol ; Nitric Oxide/metabolism ; Structure-Activity Relationship ; Up-Regulation ; Vasodilation/drug effects |
| Chemical Substances | Adrenergic beta-1 Receptor Antagonists ; Adrenergic beta-Antagonists ; Benzopyrans ; Ethanolamines ; Nebivolol (030Y90569U) ; Nitric Oxide (31C4KY9ESH) |
| Language | English |
| Publishing date | 2008 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 2428378-2 |
| ISSN | 1755-5922 ; 1755-5914 |
| ISSN (online) | 1755-5922 |
| ISSN | 1755-5914 |
| DOI | 10.1111/j.1527-3466.2008.00044.x |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 2474: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.